To evaluate the socio-economic effects of Helicobacter pylori eradication in the treatment of duodenal ulcer disease in Japan, a clinical decision analysis was performed to assess H. pylori eradication therapy compared with the conventional strategy of maintenance with histamine-2 receptor antagonists. A decision tree-based state transition model (Markov chain approach) implemented to simulate a 5 year period of follow up was constructed. The H. pylori eradication strategy was found to be superior to the conventional maintenance strategy with regard to clinical effectiveness and other dimensions of a patient's outcome. Furthermore, in a long-term perspective, the eradication strategy was less costly than the maintenance strategy. Helicobacter pylori eradication should be recommended as the first choice treatment of H. pylori-positive duodenal ulcer patients. The clinical implication of H. pylori eradication entails an improvement in clinical effectiveness and other dimensions of a patient's outcome and a significant reduction in the costs of duodenal ulcer treatment. The long-term total costs do not depend on the initial drug cost of an eradication regimen. Pursuing a high eradication rate of H. pylori is essential in improving the patient's outcome and the cost-effectiveness of treatment.