Testing for gonorrhea and chlamydia should be routinely performed.

Treatment is often with NSAIDs and antibiotics however, this is not always effective.

Treatment depends on the proximate cause. In one study, it was reported that 9 of 13 men who underwent vasectomy reversal in an attempt to relieve post-vasectomy pain syndrome became pain-free, though the followup was only one month in some cases. Another study found that 24 of 32 men had relief after vasectomy reversal.

Nerve entrapment is treated with surgery to free the nerve from the scar tissue, or to cut the nerve. One study reported that denervation of the spermatic cord provided complete relief at the first follow-up visit in 13 of 17 cases, and that the other four patients reported improvement. As nerves may regrow, long-term studies are needed.

One study found that epididymectomy provided relief for 50% of patients with post-vasectomy pain syndrome.

Orchiectomy is recommended usually only after other surgeries have failed.

A retrospective postal survey of 396 men found that 4% had significant genital pain for more than one year that required surgical intervention.

Another study contacted 470 vasectomy patients and received 182 responses, finding that 18.7% of respondents experienced chronic genital pain with 2.2% of respondents experiencing pain that adversely affected quality of life.

The most robust study of post-vasectomy pain, according to the American Urology Association's Vasectomy Guidelines 2012 (amended 2015) found a rate of 14.7% reported new-onset scrotal pain at 7 months after vasectomy with 0.9% describing the pain as "quite severe and noticeably affecting their quality of life".