Long-term maintenance therapies with proton pump inhibitor (PPI), H2receptor-antagonist (H2RA), or prokinetic agent are often utilized in patients with symptoms of gastroesophageal reflux disease (GERD) or erosive esophagitis. Maintenance therapy can be short-term symptomatic drug treatment repeated when symptoms reoccur (intermittent) or long-term continuous treatment (continuous). OBJECTIVE: To assess which maintenance treatment results in the most asymptomatic patients. For continuous treatment, to assess if the dose should be reduced (step-down therapy) or switched to another drug. METHODS: A decision tree analytic model with a one-year timeframe comparing clinical outcomes of maintenance drug treatment options with omeprazole, ranitidine, or cisapride was used. Healing rates used in the model were determined by meta-analysis of randomized clinical studies. The decision tree was constructed based on published treatment algorithms. RESULTS: For continuous treatment: at 4 months, 94% of patients taking omeprazole 20mg daily were asymptomatic versus 77% for ranitidine 300mg daily. Stepping down from omeprazole 20mg to 10mg resulted in 91% asymptomatic and switching to ranitidine 300mg daily resulted in 77% of patients asymptomatic; at 12 months, 99% of patients were asymptomatic for all continuous treatment options. However, of these, 63% had no treatment failures throughout the year for omeprazole 20 mg versus 51% for patients stepped down to omeprazole 10mg daily versus 32% for patients switched to ranitidine 300 mg daily versus 38% for patients taking ranitidine 300mg daily initially. For intermittent treatment: at 12 months, 79%, 76%, and 80% of patients were asymptomatic for omeprazole 20mg, ranitidine 300mg, and cisapride 40mg daily, respectively. CONCLUSIONS: Continuous maintenance treatment options resulted in more patients asymptomatic than intermittent treatment options. Continuous treatment with PPI resulted in more patients asymptomatic with fewer treatment failures throughout the year versus H2RA, step-down or switch therapy.