Treatment for fistula varies depending on the cause and extent of the fistula, but often involves surgical intervention combined with antibiotic therapy.

Typically the first step in treating a fistula is an examination by a doctor to determine the extent and "path" that the fistula takes through the tissue.

In some cases the fistula is temporarily covered, for example a fistula caused by cleft palate is often treated with a palatal obturator to delay the need for surgery to a more appropriate age.

Surgery is often required to assure adequate drainage of the fistula (so that pus may escape without forming an abscess). Various surgical procedures are commonly used, most commonly fistulotomy, placement of a seton (a cord that is passed through the path of the fistula to keep it open for draining), or an endorectal flap procedure (where healthy tissue is pulled over the internal side of the fistula to keep feces or other material from reinfecting the channel). Treatment involves filling the fistula with fibrin glue; also plugging it with plugs made of porcine small intestine submucosa have also been explored in recent years, with variable success. Surgery for anorectal fistulae is not without side effects, including recurrence, reinfection, and incontinence. High rate of recurrence and more chances of complications like incontinence are always there in fistula surgeries (Anal Fistula).

It is important to note that surgical treatment of a fistula without diagnosis or management of the underlying condition, if any, is not recommended. For example, surgical treatment of fistulae in Crohn's disease can be effective, but if the Crohn's disease itself is not treated, the rate of recurrence of fistula is very high (well above 50%).

The mainstay of treatment for CCF is endovascular therapy. This may be transarterial (mostly in the case of direct CCF) or transvenous (most commonly in indirect CCF). Occasionally, more direct approaches, such as direct transorbital puncture of the cavernous sinus or cannulation of the draining superior orbital vein are used when conventional approaches are not possible. Spontaneous resolution of indirect fistulae has been reported but is uncommon. Staged manual compression of the ipsilateral carotid has been reported to assist with spontaneous closure in selected cases.

Direct CCF may be treated by occlusion of the affected cavernous sinus (coils, balloon, liquid agents), or by reconstruction of the damaged internal carotid artery (stent, coils or liquid agents).

Indirect CCF may be treated by occlusion of the affected cavernous sinus with coils, liquid agents or a combination of both.

One approach used for treatment is embolization. A six-vessel angiogram is employed to determine the vascular supply to the fistula. Detachable coils, liquid embolic agents like NBCA, and onyx, or combinations of both are injected into the blood vessel to occlude the DAVF. Preoperative embolization can also be used to supplement surgery.

DAVFs are also managed surgically. The operative approach varies depending on the location of the lesion.

Stereotactic radiosurgery

Stereotactic radiosurgery is used obliterating DAVFs post-embolization, and is considered an important adjunct. Use of this method, however, is limited to benign DAVFs that have failed other treatments.

The formation of a TIF is a medical emergency and requires immediate intervention. Blood volume control, management of the hemorrhage, and adequate oxygenation should be insured in these patients. In a majority of TIF cases (85%), hyperinflation of the tracheostomy cuff will control the bleeding, while the patient is prepared for surgery. However, if this fails the tracheostomy cuff must be removed, and the patient must be intubated from above. Next, pressure from the index finger can be applied on the bleeding site from within the tracheostomy to control the bleeding. In addition, the "Utley Maneuver", which involves digital compression of the artery against the posterior wall of the manubrium of the sternum following a right infraclavicular incision, may be used to urgently control the bleeding When the bleeding is controlled the patient should be immediately transferred on the operating room.

There are several stages to treating an anal fistula:

Definitive treatment of a fistula aims to stop it recurring. Treatment depends on where the fistula lies, and which parts of the internal and external anal sphincters it crosses.

There are several options:

- Doing nothing — a drainage seton can be left in place long-term to prevent problems. This is the safest option although it does not definitively cure the fistula.

- Lay-open of fistula-in-ano — this option involves an operation to cut the fistula open. Once the fistula has been laid open it will be packed on a daily basis for a short period of time to ensure that the wound heals from the inside out. This option leaves behind a scar, and depending on the position of the fistula in relation to the sphincter muscle, can cause problems with incontinence. This option is not suitable for fistulae that cross the entire internal and external anal sphincter.

- Cutting seton — if the fistula is in a high position and it passes through a significant portion of the sphincter muscle, a cutting seton (from the Latin "seta", "bristle") may be used. This involves inserting a thin tube through the fistula tract and tying the ends together outside of the body. The seton is tightened over time, gradually cutting through the sphincter muscle and healing as it goes. This option minimizes scarring but can cause incontinence in a small number of cases, mainly of flatus. Once the fistula tract is in a low enough position it may be laid open to speed up the process, or the seton can remain in place until the fistula is completely cured. This was the traditional modality used by physicians in Ancient Egypt and formally codified by Hippocrates, who used horsehair and linen.

- Seton stitch — a length of suture material looped through the fistula which keeps it open and allows pus to drain out. In this situation, the seton is referred to as a draining seton. The stitch is placed close to the ano-rectal ring – which encourages healing and makes further surgery easy.

- Fistulotomy — till anorectal ring

- Colostomy — to allow healing

- Fibrin glue injection is a method explored in recent years, with variable success. It involves injecting the fistula with a biodegradable glue which should, in theory, close the fistula from the inside out, and let it heal naturally. This method is perhaps best tried before all others since, if successful, it avoids the risk of incontinence, and creates minimal stress for the patient.

- Fistula plug involves plugging the fistula with a device made from small intestinal submucosa. The fistula plug is positioned from the inside of the anus with suture. According to some sources, the success rate with this method is as high as 80%. As opposed to the staged operations, which may require multiple hospitalizations, the fistula plug procedure requires hospitalization for only about 24 hours. Currently, there are two different anal fistula plugs cleared by the FDA for treating ano-rectal fistulae in the United States. This treatment option does not carry any risk of bowel incontinence. In the systematic review published by Dr Pankaj Garg, the success rate of the fistula plug is 65-75%.

- Endorectal advancement flap is a procedure in which the internal opening of the fistula is identified and a flap of mucosal tissue is cut around the opening. The flap is lifted to expose the fistula, which is then cleaned and the internal opening is sewn shut. After cutting the end of the flap on which the internal opening was, the flap is pulled down over the sewn internal opening and sutured in place. The external opening is cleaned and sutured. Success rates are variable and high recurrence rates are directly related to previous attempts to correct the fistula.

- LIFT Technique is a novel modified approach through the intersphincteric plane for the treatment of fistula-in-ano, known as LIFT (ligation of intersphincteric fistula tract) procedure. LIFT procedure is based on secure closure of the internal opening and removal of infected cryptoglandular tissue through the intersphincteric approach. Essential steps of the procedure include, incision at the intersphincteric groove, identification of the intersphincteric tract, ligation of intersphincteric tract close to the internal opening and removal of intersphincteric tract, scraping out all granulation tissue in the rest of the fistulous tract, and suturing of the defect at the external sphincter muscle. The procedure was developed by Thai colorectal surgeon, Arun Rojanasakul, The first reports of preliminary healing result from the procedure were 94% in 2007. Additional ligation of the intersphincteric fistula tract did not improve the outcome after endorectal advancement flap.

- Fistula clip closure (OTSC Proctology) is the latest surgical development, which involves the closure of the internal fistula opening with a superelastic clip made of nitinol (OTSC). During surgery, the fistula tract is debrided with a special fistula brush and the clip is transanally applied with the aid of a preloaded clip applicator. The surgical principle of this technique relies on the dynamic compression and permanent closure of the internal fistula opening by the superelastic clip. Consequently, the fistula tract dries out and heals instead of being kept open by continuous feeding with stool and fecal organisms. This minimally-invasive sphincter-preserving technique has been developed and clinically implemented by the German surgeon Ruediger Prosst. First clinical data of the clip closure technique demonstrate a success rate of 90% for previously untreated fistulae and a success rate of 70% for recurrent fistulae.

- PERFACT Procedure is another latest addition to the armamentarium to treat complex and highly complex fistula-in-ano. It is a minimally cutting procedure as both the anal sphincters (internal and external sphincters) are not cut/damaged at all. Therefore, the risk of incontinence is minimal. PERFACT procedure (proximal superficial cauterization, emptying regularly fistula tracts and curettage of tracts) entails two steps: superficial cauterization of mucosa at and around the internal opening and keeping all the tracts clean. The principle is to permanently close the internal opening by granulation tissue. This is achieved by superficial electrocauterization at and around the internal opening and subsequently allowing the wound to heal by secondary intention. Early results of this procedure are quite encouraging for complex fistula-in-ano (86.4% in highly complex anal fistulae). The procedure is effective even in fistula associated with abscess, supralevator fistula-in-ano and fistula where the internal opening is non-localizable.

In people with renal failure, requiring dialysis, a cimino fistula is often deliberately created in the arm by means of a short day surgery in order to permit easier withdrawal of blood for hemodialysis.

As a radical treatment for portal hypertension, surgical creation of a portacaval fistula produces an anastomosis between the hepatic portal vein and the inferior vena cava across the omental foramen (of Winslow). This spares the portal venous system from high pressure which can cause esophageal varices, caput medusae, and hemorrhoids.

Simple cholecystectomy is suitable for type I patients. For types II–IV, subtotal cholecystectomy can be performed to avoid damage to the main bile ducts. Cholecystectomy and bilioenteric anastomosis may be required. Roux-en-Y hepaticojejunostomy has shown good outcome in some studies.

A sternal saw and a rigid bronchoscopy is used during the operation. During the operation, a median sternotomy is performed in order to expose and ligate the involved artery above and below the fistula. Division of the thymus and superior retraction of the innominate vein exposes the innominate artery. The innominate artery should be debrided to healthy tissue and closed with a monofilament suture. Next, the damaged segments of the trachea and the artery should be excised followed by reconstruction with a primary end to end anastomosis of the trachea. Innominate artery ligation leaves the carotid and subclavian circulations intact. Pulsatile back-bleeding from distal innominate artery stump should be checked to insure collateral circulation. In patients with poor pulsatile back-bleeding, an aorta-axillary artery bypass graft can be considered in patients with severe occlusion of the left common carotid artery, severe atherosclerosis, and brain ischemic or hemorrhagic insults. In addition, an autologous vein bypass between the aorta and the carotid artery or the opposite carotid artery and the subclavian artery may be performed to restore normal circulation. The interposition of viable tissue facilitates tracheal wall repair. Thus, vascularized tissues such as the thymus, strap muscles, the sternocleidomastoid, or the pectoralis major muscle should be interposed between tracheal defect and the vessel stumps to prevent bleeding, seal the mediastinum, fill dead space, cover major vital structures, provide a blood supply and venous drainage, and increase the concentration of antibiotics.

Innominate artery ligation has a 10% risk of neurological deficit.

Some people will have an active infection when they present with a fistula, and this requires clearing up before definitive treatment can be decided.

Antibiotics can be used as with other infections, but the best way of healing infection is to prevent the buildup of pus in the fistula, which leads to abscess formation. This can be done with a seton.

The procedure was invented by doctors James Cimino and M. J. Brescia in 1966. Before the Cimino fistula was invented, access was through a Scribner shunt, which consisted of a Teflon tube with a needle at each end. Between treatments, the needles were left in place and the tube allowed blood flow to reduce clotting. But Scribner shunts lasted only a few days to weeks. Frustrated by this limitation, James E. Cimino recalled his days as a phlebotomist (blood drawer) at New York City's Bellevue Hospital in the 1950s when Korean War veterans showed up with fistulas caused by trauma. Cimino recognized that these fistulas did not cause the patients harm and were easy places to get repeated blood samples. He convinced surgeon Kenneth Appell to create some in patients with chronic kidney failure and the result was a complete success. Scribner shunts were quickly replaced with Cimino fistulas, and they remain the most effective, longest-lasting method for long-term access to patients' blood for hemodialysis today.

Patients with enteric content exiting a wound on their abdomen are motivated to undergo operation. The majority will close spontaneously within approximately 6 weeks. If it has not closed by 12 weeks, it is unlikely to do so and definitive surgery should be planned. The median time to definitive repair from fistula onset was 6 months (range 1 day to 28 months). The 6-month time course is commonly utilized by groups with significant experience treating fistulas, owing to the trend in encountering a less hostile abdomen than in the early phases. Some evidence also suggests that somatostatin can be an effective treatment with respect to reducing closure time and improving the spontaneous closure rate of enterocutaneous fistulas.

Although generally benign, the cyst must be removed if the patient exhibits difficulty in breathing or swallowing, or if the cyst is infected. Even if these symptoms are not present, the cyst may be removed to eliminate the chance of infection or development of a carcinoma, or for cosmetic reasons if there is unsightly protrusion from the neck.

Thyroid scans and thyroid function studies are ordered preoperatively; this is important to demonstrate that normally functioning thyroid tissue is in its usual area.

Surgical management options include the Sistrunk procedure, en bloc central neck dissection, suture-guided transhyoid pharyngotomy, and Koempel's supra-hyoid technique. Cystectomy is an inadequate approach.

It has been suggested that suction drains placed during surgery and non-peritonisation (not closing the posterior peritoneum) may reduce the possibility of lymphocele development.

Smaller lymphoceles can be managed expectantly, and many lesions will regress over time. For symptomatic lesions a number of approaches are available and include fine needle aspiration with US or CT guidance, catheter insertion and drainage (with possible use of sclerosants), and surgical drainage. Sex and masturbation may cause the lymphocele to grow if it is in the genital area. It is suggested to avoid these activities for around one to one and a half months. Some exercises may also help to shrink it.

The radiocephalic arteriovenous fistula (RC-AVF) is a shortcut between cephalic vein and radial artery at the wrist. It is the recommended first choice for hemodialysis access. Possible underlying causes for failure are stenosis and thrombosis especially in diabetics and those with low blood flow such as due to narrow vessels, arteriosclerosis and advanced age. Reported patency of fistulae after 1 year is about 62.5%.

Many women delay treatment for decades. Surgeons often will correct the fistula through major gynecological surgery. Newer treatments can include the placement of a stent and is usually successful. In 0.5-2.5% of major pelvic surgeries a ureterovaginal fistula will form, usually weeks later. If the fistula cannot be repaired, the clinician may create a permanent diversion of urine or urostomy. Risks associated with the repair of the fistula are also associated with most other surgical procedures and include the risk of adhesions, disorders of wound healing, infection, ileus, and immobilization. There is a recurrence rate of 5%–15% in the surgical operation done to correct the fistula.

Courses of treatment typically include the following:

- Draining the pus once awhile as it can build up a strong odor

- Antibiotics when infection occurs.

- Surgical excision is indicated with recurrent fistular infections, preferably after significant healing of the infection. In case of a persistent infection, infection drainage is performed during the excision operation. The operation is generally performed by an appropriately trained specialist surgeon e.g. an otolaryngologist or a specialist General Surgeon.

- The fistula can be excised as a cosmetic operation even though no infection appeared. The procedure is considered an elective operation in the absence of any associated complications.

Aortic ruptures can be repaired surgically via open aortic surgery or using endovascular therapy (EVAR), regardless of cause, just as non-ruptured aortic aneurysms are repaired. An aortic occlusion balloon can be placed to stabilize the patient and prevent further blood loss prior to the induction of anesthesia.

The production of pancreatic enzymes is suppressed by restricting the patient's oral intake of food patient in conjunction with the use of long-acting somatostatin analogues. The patient's nutrition is maintained by total parenteral nutrition.

This treatment is continued for 2–3 weeks, and the patient is observed for improvement. If no improvement is seen, the patient may receive endoscopic or surgical treatment. If surgical treatment is followed, an ERCP is needed to identify the site of the leak.

Fistulectomy is done in which the involved part of the pancreas is also removed.

The Sistrunk procedure is the surgical resection of the central portion of the hyoid bone along with a wide core of tissue from the midline area between the hyoid and foramen cecum. It involves excision not only of the cyst but also of the path's tract and branches, and removal of the central portion of the hyoid bone is indicated to ensure complete removal of the tract. The original Sistrunk papers (the "classic" procedure described in 1920, and the "modified" procedure described in 1928) are available on-line with a modern commentary.

In general, the procedure consists of three steps:

1. incision

2. resection of cyst and hyoid bone

3. drainage and closure

There are several versions of the Sistrunk procedure, including:

- "classic": excision of the center of the hyoid bone along with a thyroglossal duct cyst, removal of one-eighth inch diameter core of tongue muscle superior to the hyoid at a 45 degree angle up to the foramen cecum to include mucosa, removal of one-quarter inch of the center of the hyoid bone, closure of the cut ends of the hyoid bone, and placement of a drain.

- modified: dissection through the tongue base but not through the mucosa. The modified Sistrunk procedure is the procedure of choice in both primary and revision cases.

- hyoid cartilage division: In cases without mature ossification of the hyoid bone, the non-fused cartilage portion can be divided by monopolar Bovie electro-cauterization or scissors. There were no statistical differences between this modified Sistrunk and the conventional Sistrunk procedure.

The procedure is relatively safe. In a study of 35 pediatric patients, Maddalozzo et. al found no major complications, but did observe minor complications (6 patients presented with seroma and 4 patients with local wound infections). A more recent paper analyzed 24 research studies on different treatment complications of thyroglossal cyst, and reported a total minor complications rate of 6% for the Sistrunk operation (classical or modified) and simple cystectomy treatment modalities. The Sistrunk procedure also showed better outcomes concerning the rate of overall recurrence, i.e. has the lowest rate of recurrence.

Sistrunk procedure results in a 95% cure rate and 95–100% long-term survival.

The nature of the injury varies depending on the size and location of the fistula, so a surgeon with experience is needed to improvise on the spot. Before the person undergoes surgery, treatment and evaluation are needed for conditions including anemia, malnutrition, and malaria. Quality treatment in low-resource settings are possible (as in the cases of Nigeria and Ethiopia).

Treatment is available through reconstructive surgery. Primary fistula repair has a 91% success rate. The corrective surgery costs about US$100 – 400, and the cost for the entire procedure, which includes the actual surgery, postoperative care, and rehabilitation support, is estimated to cost $300–450. Initial surgeries done by inadequately trained doctors and midwives increase the number of follow-up surgeries that must be performed to restore full continence. Successful surgery enables women to live normal lives and have more children, but it is recommended to have a cesarean section to prevent the fistula from recurring. Postoperative care is vital to prevent infection. Some women are not candidates for this surgery due to other health problems. In those cases, fecal diversion can help the patient, but not necessarily cure them.

Besides physical treatment, mental health services are also needed to rehabilitate fistula patients, who experience psychological trauma from being ostracized by the community and from fear of developing fistulae again. A study on the first formal counseling program for fistula survivors in Eritrea shows positive results, whereby counseling significantly improved the women's self-esteem, knowledge about fistulae and fistula prevention, and behavioral intentions for "health maintenance and social reintegration" following surgery.

Challenges with regards to treatment include the very high number of women needing reconstructive surgery, access to facilities and trained surgeons, and the cost of treatment. For many women, US$300 is an impossible price and they cannot afford the surgery. Access and availability of treatment also vary widely across different sub-Saharan countries. Certain regions also do not have enough maternal care clinics that are equipped, willing to treat fistula patients, and adequately staffed. At the Evangelical Hospital of Bemberéke in Benin, only one expatriate volunteer obstetrics and gynecology doctor is available a few months per year, with one certified nurse and seven informal hospital workers. In all of Niger, two medical centers treat fistula patients. In Nigeria, more dedicated health professionals operate on up to 1,600 women with a fistula per year. The world is currently severely under capacity for treating the problem; it would take up to 400 years to treat the backlog of patients. To prevent any new cases of obstetric fistulae, about 75,000 new emergency obstetric care facilities would have to be built in Africa alone, plus an increase in financial support and an even higher number of certified doctors, midwives, and nurses needed.

Another challenge standing between women and fistula treatment is information. Most women have no idea that treatment is available. Because this is a condition of shame and embarrassment, most women hide themselves and their condition and suffer in silence. In addition, after receiving initial treatment, health education is important to prevent fistulae in subsequent pregnancies.

Another challenge is the lack of trained professionals to provide surgery for fistula patients. As a result, nonphysicians are sometimes trained to provide obstetric services. For example, the Addis Ababa Fistula Hospital has medical staff without formal degrees, and one of its top surgeons was illiterate, but she had been trained over years and now regularly successfully performs fistula surgery.

Colostomy is recommended by most surgeons, and has a good prognosis, with 90% of patients regaining normal bowel control. Since the rectal opening and anal orifice in a vestibular fistula tend to be short and narrow, a colostomy is usually performed to allow decompression of the bowel unless the orifice is wide enough to allow normal defecation. Colostomy is often followed by posterior sagittal anorectoplasty (PSARP), a surgical procedure to repair the anal orifice, at a later date. Some surgeons prefer to perform an immediate PSARP without a colostomy first, while others perform neither a colostomy nor a PSARP and instead opt for a simple dilatation of the orifice to allow stool to pass and the bowel to decompress. It has been suggested that only experienced surgeons should perform repair without an initial colostomy.

After diagnosing rectovaginal fistula, it is best to wait for around 3 months to allow the inflammation to subside. For low fistulae, a vaginal approach is best, while an abdominal repair would be necessary for a high fistula at the posterior fornix.

A circular incision is made around the fistula and vagina is separated from the underlying rectum with a sharp circumferential dissection. The entire fistulous tract, along with a small rim of rectal mucosa is incised. The rectal wall is then closed extramucosally.

Most rectovaginal fistuals will need surgery to fix. Medications such as antibiotics and Infliximab might be prescribed to help close the rectovaginal fistula or prepare for surgery.

If bacterial infection is suspected, antibiotics may be used. Despite being recommended by several guidelines, the use of antibiotics in mild cases of uncomplicated diverticulitis is supported with only "sparse and of low quality" evidence, with no evidence supporting their routine use.