OBJECTIVE: This review was to evaluate the efficacy and toxicity of radiation therapy (RT) administered immediately after hyperbaric oxygen (HBO) therapy in patients with high grade gliomas. RESEARCH DESIGN AND METHODS: PubMed, Embase, ISI Web of Knowledge, and Cochrane databases were searched using combinations of the following search terms: radiotherapy, hyperbaric oxygenation, chemotherapy, glioma, brain tumor. Selection was limited to prospective studies involving patients given HBO followed by RT for high-grade gliomas. Data extracted from studies included the clinical research phase of the study, number of study arms, number of patients, patient age and gender, glioma type and grade, pressure and length of HBO, protocol of radiation therapy, duration of follow-up, and the outcomes. MAIN OUTCOME MEASURES: Overall survival, time to progression, response rate, tumor regression, and toxic effects associated with HBO plus RT treatment. RESULTS: Literature search/screening yielded eight studies for analysis. Six of the studies were single-arm in design and enrolled a total of 203 patients, of whom 142 had grade IV gliomas and 61 had grade III gliomas. In these six studies, all patients received HBO then RT. Two studies were double-arm in design, with 24 patients treated with HBO followed by RT and 26 patients treated with RT alone. The findings from both the single- and double-arm studies indicated improved outcomes (survival rate, progression free survival, time to progression, response rate) with HBO and RT therapy. Reported toxicity included leucopenia, anemia, thrombocytopenia, fever, loss of appetite, constipation, nausea, vomiting, and liver dysfunction. The addition of HBO had minimal effect on toxicity or side effects; across the eight studies, only one patient with severe middle ear barotrauma had a complication directly related to HBO exposure. CONCLUSION: This systematic reviews suggests that the addition of HBO to RT is tolerated and may be beneficial in patients with high-grade gliomas.