Chronic radiation injuries, although uncommon, are associated with poor quality of life in oncology patients. The present study assesses the efficacy and safety of hyperbaric oxygen therapy in the management of chronic radiation-induced tissue injuries.A retrospective analysis was performed in 276 consecutive patients treated with hyperbaric oxygen therapy for chronic radiation-induced tissue injuries at the Hyperbaric Medicine Unit, Townsville, Queensland, between March 1995 and March 2008. Of these patients, 189 (68%) had complete follow-up data and were assessed.A total of 265 events of chronic radiation tissue injury were experienced by the 189 patients treated with hyperbaric oxygen therapy. Osteoradionecrosis prophylaxis due to radiation-induced dental disease had an overall response rate of 96% (P=0.00003; Wilcoxon matched-pairs signed-rank test). The overall response rates for established osteoradionecrosis of mandible, soft tissue necrosis of head and neck, and xerostomia were 86% (P=0.00001), 85% (P=0.002) and 64% (P=0.0001), respectively. The overall response rates for soft tissue necrosis at other sites, chronic radiation proctitis and hemorrhagic cystitis were 84% (P=0.03), 95% (P=0.0001) and 85% (P=0.03), respectively. The total complication rate after hyperbaric oxygen therapy was 15.9%, comprising reversible ear barotrauma (10.6%), reversible ocular barotrauma (4.2%), dental complications (0.5%) and myocardial infarction (0.5%).Our study demonstrates that hyperbaric oxygen therapy can be effectively used in a variety of chronic radiation-induced tissue injuries; its favorable risk profile suggests it should be considered for patients with radiation-induced tissue injuries.