Recently, the third proton pump inhibitor (PPI), Rabeprazole, has been marketed in Japan. However, its economic aspect has not been studied. OBJECTIVE: The purpose of this study was to compare the cost-effectiveness of three PPIs for the treatment of gastric ulcer. METHOD: We constructed the treatment model for gastric ulcer treatment, and compared the cost and healed days of three PPIs, Lansoprazole, Omeprazole and Rabeprazole, and Famotidine, a histamine2 blocker. Since the approved maximum treatment duration was 8 weeks for PPIs, the time horizon of this study was set to 8 weeks. The healing rates at 2, 4, 6 and 8 weeks were taken from the independent randomized controlled trials. In these trials, the comparator was Famotidine and the endpoint was endoscopically confirmed healing. The fee schedule set by the Japanese Ministry of Health and Welfare was used for cost calculation. RESULTS: Incremental cost compared to Famotidine were -3,936 yen for Lansoprazole, +1,240 yen for Omeprazole and -6,037 yen for Rabeprazole. Incremental healed days compared to Famotidine were 8.9, 3.7 and 11.3 days respectively. Therefore, the treatment by Rabeprazole was the least expensive and the most effective among the three PPIs. CONCLUSION: Among the PPIs available in Japan, Rabeprazole was considered to be the most cost-effective treatment option for gastric ulcer.