Late radiation proctopathy is a painful and vexing complication of prostate radiation. We report a case of a 55-year-old man with prostate cancer, and complaints of tenesmus and severe rectal pain after radiation therapy. The patient was diagnosed with a locally advanced Gleason score 8 prostate cancer and an increased prostate-specific antigen of 42.3 ng/ml. His past medical history was notable for a history of bilateral lymph node dissection complicated by Clostridium difficile colitis. He subsequently received 3-dimensional conformal radiation therapy. Seven months after completing therapy, minor rectal bleeding and significant pain developed, requiring increasing doses of opioid analgesics. Fourteen months after 3-dimensional conformal radiation therapy, sigmoidoscopy revealed a single chronic deep ulcer at the anorectal junction. As an alternative to diverting colostomy, the patient underwent a course of hyperbaric oxygen. Within 1 month of completing hyperbaric oxygen treatment, his symptoms completely resolved. Nine months from completion of hyperbaric oxygen therapy, he has had no recurrence of symptoms. Hyperbaric oxygen therapy can be considered a treatment option after failure of standard treatments in patients with severe radiation proctopathy.