Carbon monoxide (CO) poisoning results in not only severe psychoneurological disorders, but can also cause secondary delayed psychoneurological disorders. Therefore, timely and appropriate treatment in the acute stage is crucial to prevent such direct neurological damage and secondary disorders. However, various conflicting results have been reported in studies of CO poisoning treatment, and the efficacy of hyperbaric oxygen therapy (HBO2T) for CO poisoning has not been established. This retrospective multi-institutional study was performed by the questionnaire in 1667 cases of acute CO poisoning in Japan. The effectiveness of HBO2T for CO poisoning was evaluated based on prognoses in cases and various classes of hospital based on the grade of their positive stance regarding HBO2T. The results showed that the prognosis in the group treated with HBOT was significantly better than that in the group treated with normobaric oxygen therapy (NBO2T) (P < 0.01), thus confirming the effectiveness of HBO2T for CO poisoning. Furthermore, while hospitals were separated into three groups according to their indication criteria for HBO2T, the ineffective ratio of NBO2T was dependent on the indication criteria, even though the effective ratio of HBO2T was the same in all three groups. In conclusion, a retrospective multi-institutional study showed that HBO2T is an effective form of therapy for CO poisoning.