OBJECTIVE Radiation therapy has been used successfully to treat pelvic malignancy but morbidity from hemorrhagic cystitis remains a major long-term sequela in 1 to 2% of patients. Obliterative endarteritis secondary to ionizing radiation leads to tissue hypoxia and poor healing. Hyperbaric oxygen therapy has been demonstrated to improve angiogenesis and promote healing in radiation injured tissue, including the bladder. We describe the treatment and long-term followup of a cohort of patients treated with hyperbaric oxygen for hemorrhagic cystitis. METHODS A total of 17 patients (mean age 62 years) with hemorrhagic cystitis received hyperbaric oxygen following failure of standard treatment modalities. Hyperbaric oxygen was administered on a once daily schedule (mean number of treatments 14) until hematuria resolved. Followup ranged from 9 to 60 months (mean 21). RESULTS Hematuria resolved completely in 11 of 17 patients (64%), 2 had only residual microscopic hematuria, 2 had improvement but died of complications relating to cancer shortly after completion of treatment and 2 had recurrence of gross hematuria. Early application of hyperbaric oxygen was associated with earlier resolution of hemorrhagic cystitis. CONCLUSIONS Radiation induced hemorrhagic cystitis that does not respond to standard regimens can be successfully treated with hyperbaric oxygen. This modality is well tolerated even in patients debilitated by advanced cancer and blood loss. Long-term remission can be achieved in the majority of patients.