The relative cost-effectiveness of proton-pump inhibitors (PPIs) in the maintenance therapy of erosive reflux esophagitis was studied. Decision analysis was used to model the cost-effectiveness of PPIs on the basis of clinical trial results. Management decisions in the model were based on published U.S. guidelines and recommendations. Probability estimates were derived from a systematic review of the literature. The model's base-case scenario compared rabeprazole, lansoprazole, and omeprazole for the prevention of symptom recurrence over one year. Meta-analyzed estimates of efficacy were derived from trials by using a generalized logistic regression model with random effects. Medical costs for hospitalization, procedures, and office visits reflected 2000 Medicare payment; drug costs were based on 2000 average wholesale prices. Average costs per patient were comparable among the PPIs (rabeprazole, $1414; lansoprazole, $1671; and omeprazole, $1599). Rabeprazole prevented symptom recurrence in 86% of rabeprazole recipients, versus 68% for lansoprazole and 81% for omeprazole, and yielded the lowest average cost-effectiveness ratio (rabeprazole, $1637 per recurrence prevented; lansoprazole, $2439; and omeprazole, $1968). The model was robust to changes in key variables. When evaluated by decision analysis over a wide range of assumptions, rabeprazole was comparable to other PPIs in terms of cost and offered improved effectiveness for maintenance therapy of erosive reflux esophagitis.