Warfarin and vitamin K antagonists are anticoagulants that can be taken orally to reduce thromboembolic occurrence. Where a more effective response is required, heparin can be given (by injection) concomitantly. As a side effect of any anticoagulant, the risk of bleeding is increased, so the international normalized ratio of blood is monitored. Self-monitoring and self-management are safe options for competent patients, though their practice varies. In Germany, about 20% of patients were self-managed while only 1% of U.S. patients did home self-testing (according to one 2012 study). Other medications such as direct thrombin inhibitors and direct Xa inhibitors are increasingly being used instead of warfarin.

Recommendations for those without cancer include anticoagulation (stopping further blood clots from forming) with dabigatran, rivaroxaban, apixaban, or edoxaban rather than warfarin or low molecular weight heparin (LMWH). For those with cancer LMWH is recommended. For initial treatment of VTE, fixed doses with LMWH may be more effective than adjusted doses of unfractionated heparin (UFH) in reducing blood clots. No differences in mortality, prevention of major bleeding, or preventing VTEs from recurring were observed between LMWH and UFH. No differences have been detected in the route of administration of UFH (subcutaneous or intravenous). LMWH is usually administered by a subcutaneous injection, and a persons blood clotting factors do not have to be monitored as closely as with UFH. People with cancer have a higher risk of experiencing reoccurring VTE episodes ("recurrent VTE"), despite taking preventative anticoagulation medication. These people should be given therapeutic doses of LMWH medication, either by switching from another anticoagulant or by taking a higher dose of LMWH.

For those with a small pulmonary embolism and few risk factors, no anticoagulation is needed. Anticoagulation is; however, recommended in those who do have risk factors. Thrombolysis is recommended in those with PEs that are causing low blood pressure.

Thrombolysis is the pharmacological destruction of blood clots by administering thrombolytic drugs including recombitant tissue plasminogen activator, which enhances the normal destruction of blood clots by the body's enzymes. This carries an increased risk of bleeding so is generally only used for specific situations (such as severe stroke or a massive pulmonary embolism).

Evidence-based clinical guidelines were published in 2016 for the treatment of VTE.

Treatment is aimed at controlling symptoms and improving the interrupted blood flow to the affected area of the body.

Medications include:

- Antithrombotic medication. These are commonly given because thromboembolism is the major cause of arterial embolism. Examples are:

- Anticoagulants (such as warfarin or heparin) and antiplatelet medication (such as aspirin, ticlopidine, and clopidogrel) can prevent new clots from forming

- Thrombolytics (such as streptokinase) can dissolve clots

- Painkillers given intravenously

- Vasodilators to relax and dilate blood vessels.

Appropriate drug treatments successfully produces thrombolysis and removal of the clot in 50% to 80% of all cases.

Antithrombotic agents may be administered directly onto the clot in the vessel using a flexible catheter ("intra-arterial thrombolysis"). Intra-arterial thrombolysis reduces thromboembolic occlusion by 95% in 50% of cases, and restores adequate blood flow in 50% to 80% of cases.

Surgical procedures include:

- Arterial bypass surgery to create another source of blood supply

- Embolectomy, to remove the embolus, with various techniques available:

- Thromboaspiration

- Angioplasty with balloon catheterization with or without implanting a stent Balloon catheterization or open embolectomy surgery reduces mortality by nearly 50% and the need for limb amputation by approximately 35%.

- Embolectomy by open surgery on the artery

If extensive necrosis and gangrene has set in an arm or leg, the limb may have to be amputated. Limb amputation is in itself usually remarkably well tolerated, but is associated with a substantial mortality (~50%), primarily because of the severity of the diseases in patients where it is indicated.

How well a patient does depends on the location of the clot and to what extent the clot has blocked blood flow. Arterial embolism can be serious if not treated promptly.

Without treatment, it has a 25% to 30% mortality rate. The affected area can be permanently damaged, and up to approximately 25% of cases require amputation of an affected extremity.

Arterial emboli may recur even after successful treatment.

Anticoagulant therapy is the mainstay of treatment. Acutely, supportive treatments, such as oxygen or analgesia, may be required. People are often admitted to hospital in the early stages of treatment, and tend to remain under inpatient care until the INR has reached therapeutic levels. Increasingly, however, low-risk cases are managed at home in a fashion already common in the treatment of DVT. Evidence to support one approach versus the other is weak.

Usually, anticoagulant therapy is the mainstay of treatment. Unfractionated heparin (UFH), low molecular weight heparin (LMWH), or fondaparinux is administered initially, while warfarin, acenocoumarol, or phenprocoumon therapy is commenced (this may take several days, usually while the patient is in the hospital). LMWH may reduce bleeding among people with pulmonary embolism as compared to UFH according to a systematic review of randomized controlled trials by the Cochrane Collaboration. According to the same review, LMWH reduced the incidence of recurrent thrombotic complications and reduced thrombus size when compared to heparin. There was no difference in overall mortality between participants treated with LMWH and those treated with unfractionated heparin.

Warfarin therapy often requires a frequent dose adjustment and monitoring of the international normalized ratio (INR). In PE, INRs between 2.0 and 3.0 are generally considered ideal. If another episode of PE occurs under warfarin treatment, the INR window may be increased to e.g. 2.5–3.5 (unless there are contraindications) or anticoagulation may be changed to a different anticoagulant e.g. LMWH.

In patients with an underlying malignancy, therapy with a course of LMWH is favored over warfarin; it is continued for six months, at which point a decision should be reached whether ongoing treatment is required.

Similarly, pregnant women are often maintained on low molecular weight heparin until at least six weeks after delivery to avoid the known teratogenic effects of warfarin, especially in the early stages of pregnancy.

Warfarin therapy is usually continued for 3–6 months, or "lifelong" if there have been previous DVTs or PEs, or none of the usual risk factors is present. An abnormal D-dimer level at the end of treatment might signal the need for continued treatment among patients with a first unprovoked pulmonary embolus. For those with small PEs (known as subsegmental PEs) the effects of anticoagulation is unknown as it has not been properly studied as of 2014.

Anticoagulation, which prevents further coagulation, but does not act directly on existing clots, is the standard treatment for DVT. Balancing risk vs. benefit is important in determining the duration of anticoagulation, and three months is generally the standard length of treatment. In those with an annual risk of VTE in excess of 9%, as after an unprovoked episode, extended anticoagulation is a possibility. Those who finish VKA treatment after idiopathic VTE with an elevated D-dimer level show an increased risk of recurrent VTE (about 9% vs about 4% for normal results), and this result might be used in clinical decision-making. Thrombophilia test results rarely play a role in the length of treatment.

For acute cases in the leg, the ACCP recommended a parenteral anticoagulant (such as LMWH, fondaparinux, or unfractionated heparin) for at least five days and a VKA, the oral anticoagulant, the same day. LMWH and fondaparinux are suggested over unfractionated heparin, but both are retained in those with compromised kidney function, unlike unfractionated heparin. The VKA is generally taken for a minimum of three months to maintain an international normalized ratio of 2.0–3.0, with 2.5 as the target. The benefit of taking a VKA declines as the duration of treatment extends, and the risk of bleeding increases with age.

The ACCP recommended treatment for three months in those with proximal DVT provoked by surgery. A three-month course is also recommended for those with proximal DVT provoked by a transient risk factor, and three months is suggested over lengthened treatment when bleeding risk is low to moderate. Unprovoked DVT patients should have at least three months of anticoagulation and be considered for extended treatment. Those whose first VTE is an unprovoked proximal DVT are suggested for anticoagulation longer than three months unless there is a high risk of bleeding. In that case, three months is sufficient. Those with a second unprovoked VTE are recommended for extended treatment when bleeding risk is low, suggested for extended treatment when bleeding risk is moderate, and suggested for three months of anticoagulation in high-risk scenarios.

The ACCP recommended initial home treatment instead of hospital treatment for those with acute leg DVT. This applies as long as individuals feel ready for it, and those with severe leg symptoms or comorbidities would not qualify. An appropriate home environment is expected: one that can provide a quick return to the hospital if necessary, support from family or friends, and phone access.

In addition to anticoagulation, the ACCP suggested graduated compression stockings—which apply higher pressure (30–40 mm Hg) at the ankles and a lower pressure around the knees—for those with symptomatic DVT. Use should begin as soon as possible after anticoagulation. Evidence however does not support that these stockings reduce the risk of post-thrombotic syndrome nor do they indicate a reduction in recurrent VTE. Use is suggested for two years, though inconvenience and discomfort can reduce compliance. Walking is also suggested for those without severe pain or edema.

Unless a person has medical problems preventing movement, after a person starts anti-coagulation therapy bed rest should not be used to treat acute deep vein thrombosis. There are clinical benefits associated with walking and no evidence that walking is harmful, but people with DVT are harmed by bed rest except when it is medically necessary.

Instead of anticoagulation, a follow-up imaging test (typically ultrasound) about one-week post-diagnosis is an option for those with an acute isolated distal DVT without a high risk for extension; if the clot does not grow, the ACCP does not recommend anticoagulation. This technique can benefit those at a high risk for bleeding. Patients may choose anticoagulation over serial imaging, however, to avoid the inconvenience of another scan if concerns about the risk of bleeding are insignificant. When applied to symptomatic patients with a negative initial ultrasound result, serial testing is inefficient and not cost effective.

Treatment for Thrombotic Storm may include lifelong anticoagulation therapy and/or thrombolytic therapy, plasmapherisis, and corticosteroids. Studies have shown that when anticoagulant therapy is withheld recurrence of thrombosis usually follows. INR is closely monitored in the course of treatment.

Various studies have investigated the use of anticoagulation to suppress blood clot formation in cerebral venous sinus thrombosis. Before these trials had been conducted, there had been a concern that small areas of hemorrhage in the brain would bleed further as a result of treatment; the studies showed that this concern was unfounded. Clinical practice guidelines now recommend heparin or low molecular weight heparin in the initial treatment, followed by warfarin, provided there are no other bleeding risks that would make these treatments unsuitable. Some experts discourage the use of anticoagulation if there is extensive hemorrhage; in that case, they recommend repeating the imaging after 7–10 days. If the hemorrhage has decreased in size, anticoagulants are started, while no anticoagulants are given if there is no reduction.

The duration of warfarin treatment depends on the circumstances and underlying causes of the condition. If the thrombosis developed under temporary circumstances (e.g. pregnancy), three months are regarded as sufficient. If the condition was unprovoked but there are no clear causes or a "mild" form of thrombophilia, 6 to 12 months is advised. If there is a severe underlying thrombosis disorder, warfarin treatment may need to continue indefinitely.

Thrombolysis (removal of the blood clot with "clot buster" medication) has been described, either systemically by injection into a vein or directly into the clot during angiography. The 2006 European Federation of Neurological Societies guideline recommends that thrombolysis is only used in patients who deteriorate despite adequate treatment, and other causes of deterioration have been eliminated. It is unclear which drug and which mode of administration is the most effective. Bleeding into the brain and in other sites of the body is a major concern in the use of thrombolysis. American guidelines make no recommendation with regards to thrombolysis, stating that more research is needed.

Raised intracranial pressure, if severe or threatening vision, may require therapeutic lumbar puncture (removal of excessive cerebrospinal fluid), medication (acetazolamide), or neurosurgical treatment (optic nerve sheath fenestration or shunting). In certain situations, anticonvulsants may be used to try to prevent seizures. These situations include focal neurological problems (e.g. inability to move a limb) and focal changes of the brain tissue on CT or MRI scan. Evidence to support or refute the use of antiepileptic drugs as a preventive measure, however, is lacking.

Standard medical treatment consists of anticoagulants (blood thinners), diuretics, and oxygen. Lifelong anticoagulation is recommended, even after PEA. Routine inferior vena cava filter placement is not recommended.

In patients with non-operable CTEPH or persistent/recurrent PH after PEA, there is evidence for benefit from pulmonary vasodilator drug treatment. The microvascular disease component in CTEPH has provided the rationale for off-label use of drugs approved for PAH. Currently, only riociguat (a stimulator of soluble guanylate cyclase) is approved for treatment of adults with inoperable CTEPH or persistent or recurrent CTEPH after surgical treatment. Other drug trials are ongoing in patients with inoperable CTEPH, with macitentan recently proving efficacy and safety in MERIT

Decision making for patients with CTEPH can be complex and needs to be managed by CTEPH teams in expert centres. CTEPH teams comprise cardiologists and pulmonologists with specialist PH training, radiologists, experienced PEA surgeons with a significant caseload of CTEPH patients per year and physicians with percutaneous interventional expertise. Currently, there are three recognised targeted treatment options available: pulmonary endarterectomy (PEA), balloon pulmonary angioplasty (BPA) and pulmonary vasodilator drug treatment for inoperable patients.

Specialist imaging using either magnetic resonance or invasive PA is necessary to determine risks and benefits of interventional treatment with PEA or BPA.

Those unsuitable for surgery may receive thrombolytics. In the past, streptokinase was the main thrombolytic chemical. More recently, drugs such as tissue plasminogen activator, urokinase, and anisterplase have been used in its place. Mechanical methods of injecting the thrombolytic compounds have improved with the introduction of pulsed spray catheters—which allow for a greater opportunity for patients to avoid surgery. Pharmacological thrombolysis requires a catheter insert into the affected area, attached to the catheter is often a wire with holes to allow for a wider dispersal area of the thrombolytic agent. These agents lyse the ischemia-causing thrombus quickly and effectively. However, the efficacy of thrombolytic treatment is limited by hemorrhagic complications. Plasma fibrinogen level has been proposed as a predictor of these hemorrhagic complications. However, based on a systemtic review of the available literature until January 2016, the predictive value of plasma is unproven.

Treatment for this condition entails the maintenance of intravascular volume. Additionally, the following can be done as a means of managing FES in an individual:

- Albumin can be used for volume resuscitation

- Long bone fractures should be attended to immediately (surgery)

- Mechanical ventilation

Treatment of an episode of cholesterol emboli is generally symptomatic, i.e. it deals with the symptoms and complications but cannot reverse the phenomenon itself. In kidney failure resulting from cholesterol crystal emboli, statins (medication that reduces cholesterol levels) have been shown to halve the risk of requiring hemodialysis.

In terms of treatment for this condition the individual may be advised to do the following: "raise" the affected area to decrease swelling, and relieve pressure off of the affected area so it will encounter less pain. In certain circumstances drainage of the clot might be an option. In general, treatment may include the following:

The primary intervention in acute limb ischaemia is emergency embolectomy using a Fogarty Catheter, providing the limb is still viable within the 4-6h timeframe. Other options include a vascular bypass to route blood flow around the clot.

There is no specific treatment for thrombophilia, unless it is caused by an underlying medical illness (such as nephrotic syndrome), where the treatment of the underlying disease is needed. In those with unprovoked and/or recurrent thrombosis, or those with a high-risk form of thrombophilia, the most important decision is whether to use anticoagulation medications, such as warfarin, on a long-term basis to reduce the risk of further episodes. This risk needs to weighed against the risk that the treatment will cause significant bleeding, as the reported risk of major bleeding is over 3% per year, and 11% of those with major bleeding may die as a result.

Apart from the abovementioned forms of thrombophilia, the risk of recurrence after an episode of thrombosis is determined by factors such as the extent and severity of the original thrombosis, whether it was provoked (such as by immobilization or pregnancy), the number of previous thrombotic events, male sex, the presence of an inferior vena cava filter, the presence of cancer, symptoms of post-thrombotic syndrome, and obesity. These factors tend to be more important in the decision than the presence or absence of a detectable thrombophilia.

Those with antiphospholipid syndrome may be offered long-term anticoagulation after a first unprovoked episode of thrombosis. The risk is determined by the subtype of antibody detected, by the antibody titer (amount of antibodies), whether multiple antibodies are detected, and whether it is detected repeatedly or only on a single occasion.

Women with a thrombophilia who are contemplating pregnancy or are pregnant usually require alternatives to warfarin during pregnancy, especially in the first 13 weeks, when it may produce abnormalities in the unborn child. Low molecular weight heparin (LMWH, such as enoxaparin) is generally used as an alternative. Warfarin and LMWH may safely be used in breastfeeding.

When women experience recurrent pregnancy loss secondary to thrombophilia, some studies have suggested that low molecular weight heparin reduces the risk of miscarriage. When the results of all studies are analysed together, no statistically signifiant benefit could be demonstrated.

Oxygen consumption of skeletal muscle is approximately 50 times larger while contracting than in the resting state. Thus, resting the affected limb should delay onset of infarction substantially after arterial occlusion.

Low molecular weight heparin is used to reduce or at least prevent enlargement of a thrombus, and is also indicated before any surgery. In the legs, below the inguinal ligament, percutaneous aspiration thrombectomy is a rapid and effective way of removing thromboembolic occlusions. Balloon thrombectomy using a Fogarty catheter may also be used. In the arms, balloon thrombectomy is an effective treatment for thromboemboli as well. However, local thrombi from atherosclerotic plaque are harder to treat than embolized ones. If results are not satisfying, another angiography should be performed.

Thrombolysis using analogs of tissue plasminogen activator (tPA) may be used as an alternative or complement to surgery. Where there is extensive vascular damage, bypass surgery of the vessels may be necessary to establish other ways to supply the affected parts.

Swelling of the limb may cause inhibited flow by increased pressure, and in the legs (but very rarely in the arms), this may indicate a fasciotomy, opening up all four leg compartments.

Because of the high recurrence rates of thromboembolism, it is necessary to administer anticoagulant therapy as well. Aspirin and low molecular weight heparin should be administered, and possibly warfarin as well. Follow-up includes checking peripheral pulses and the arm-leg blood pressure gradient.

Treatment with compression stockings should be offered to patients with lower extremity superficial phlebitis, if not contraindicated (e.g., peripheral artery disease). Patients may find them helpful for reducing swelling and pain once the acute inflammation subsides.

Nonsteroidal anti-inflammatory drugs (NSAID) are effective in relieving the pain associated with venous inflammation and were found in a randomized trial to significantly decrease extension and/or recurrence of superficial vein thrombosis.

Anticoagulation for patients with lower extremity superficial thrombophlebitis at increased risk for thromboembolism (affected venous segment of ≥5 cm, in proximity to deep venous system, positive medical risk factors).

Treatment with fondaparinux reduces the risk of subsequent venous thromboembolism.

Surgery reserved for extension of the clot to within 1 cm of the saphenofemoral junction in patients deemed unreliable for anticoagulation, failure of anticoagulation and patients with intense pain. Surgical therapy with ligation of saphenofemoral junction or stripping of thrombosed superficial veins appears to be associated higher rates of venous thromboembolism compared with treatment with anitcoagulants.

Oxygen first aid treatment is useful for suspected gas embolism casualties or divers who have made fast ascents or missed decompression stops. Most fully closed-circuit rebreathers can deliver sustained high concentrations of oxygen-rich breathing gas and could be used as an alternative to pure open-circuit oxygen resuscitators. However pure oxygen from an oxygen cylinder through a Non-rebreather mask is the optimal way to deliver oxygen to a decompression illness patient.

Recompression is the most effective, though slow, treatment of gas embolism in divers. Normally this is carried out in a recompression chamber. As pressure increases, the solubility of a gas increases, which reduces bubble size by accelerating absorption of the gas into the surrounding blood and tissues. Additionally, the volumes of the gas bubbles decrease in inverse proportion to the ambient pressure as described by Boyle's law. In the hyperbaric chamber the patient may breathe 100% oxygen, at ambient pressures up to a depth equivalent of 18 msw. Under hyperbaric conditions, oxygen diffuses into the bubbles, displacing the nitrogen from the bubble and into solution in the blood. Oxygen bubbles are more easily tolerated. Diffusion of oxygen into the blood and tissues under hyperbaric conditions supports areas of the body which are deprived of blood flow when arteries are blocked by gas bubbles. This helps to reduce ischemic injury. The effects of hyperbaric oxygen also counteract the damage that can occur with reperfusion of previously ischemic areas; this damage is mediated by leukocytes (a type of white blood cell).

Surgery to remove the clot is possible, but rarely performed. In the past, surgical removal of the renal vein clot was the primary treatment but it is very invasive and many complications can occur. In the past decades, treatment has shifted its focus from surgical intervention to medical treatments that include intravenous and oral anticoagulants. The use of anticoagulants may improve renal function in RVT cases by removing the clot in the vein and preventing further clots from occurring. Patients already suffering from nephrotic syndrome may not need to take anticoagulants. In this case, patients should keep an eye out and maintain reduced level of proteinuria by reducing salt and excess protein, and intaking diuretics and statins. Depending on the severity of RVT, patients may be on anticoagulants from a year up to a lifetime. As long as the albumen levels in the bloodstream are below 2.5g/L, it is recommended that RVT patients continue taking anticoagulants. Main anticoagulants that can be used to treat RVT include warfarin and low molecular weight heparin. Heparin has become very popular, because of its low risk of complications, its availability and because it can easily be administered. Warfarin is known to interact with many other drugs, so careful monitoring is required. If a nephrotic syndrome patient experiences any of the RVT symptoms (flank or back pain, blood in the urine or decreased renal function), he or she should immediately see a doctor to avoid further complications.

The main side effect of anticoagulants is the risk of excessive bleeding. Other side effects include: blood in the urine or feces, severe bruising, prolonged nosebleeds (lasting longer than 10 minutes), bleeding gum, blood in your vomit or coughing up blood, unusual headaches, sudden severe back pain, difficulty breathing or chest pain, in women, heavy or increased bleeding during the period, or any other bleeding from the vagina. Warfarin can cause rashes, diarrhea, nausea (feeling sick) or vomiting, and hair loss. Heparin can cause hair loss (alopecia) thrombocytopenia – a sudden drop in the number of platelets in the blood.

It has been reported in a case study of 27 patients with nephrotic syndrome caused RVT, there was a 40% mortality rate, mostly due to hemorrhagic complications and sepsis. In 75% of the remaining surviving patients, the RVT was resolved and renal function returned to normal. It has been concluded that age is not a factor on the survival of RVT patients, although older patient (55 and older) are more likely to develop renal failure. Heparin is crucial in returning normal renal function; in patients that did not take heparin, long term renal damage was observed in 100%. In patients that did take heparin, renal damage was observed in about 33%. By quickly treating, and receiving the correct medications, patients should increase their chances of survival and reduce the risk of the renal vein clot from migrating to another part of the body.

Treatments include anticoagulants, shunts, bypass surgery, and transplants.