Abstract: We treated two cases of interstitial cystitis (IC) that were resistant to some conventional therapies with hyperbaric oxygen (HBO). Both patients underwent 20 sessions of 100% oxygen inhalation (2.0 atmosphere absolute for 60 min/day × 5 days/week for 4 weeks) in a hyperbaric chamber. The period of follow up was 12 months for case 1 and 9 months for case 2. After a course of HBO, the bladder mucosal ulcer (Hunner's ulcer) disappeared, and changes from baseline in pain and urinary frequency was constitutively inhibited. There were no adverse events during the 20 treatment sessions. One woman (case 1) had mild Eustachian tube dysfunction, resulting in a transient hearing impairment. HBO seems to be an option for treatment of IC resistant to conventional therapies.