OBJECTIVE Patients with reflux esophagitis have rapid relapses after treatment withdrawal. This study was designed to investigate the relapse rate of symptomatic esophagitis during maintenance treatment with omeprazole versus ranitidine after the induction of acute healing with omeprazole. METHODS Patients with endoscopically verified acute erosive or ulcerative esophagitis (grade 2 or 3) were initially treated with 20 mg of omeprazole daily for 4, 8, or 12 weeks. After healing, the patients were randomized to maintenance treatment with omeprazole (20 mg every morning) or ranitidine (150 mg twice daily). A control endoscopy was performed at the end of the healing phase and after 6 months of maintenance treatment or symptomatic relapse. RESULTS Of 231 initially treated patients, 223 were healed (no erosive esophagitis) and entered the maintenance study. The estimated proportions of patients in remission after 6 months of maintenance treatment with 20 mg of omeprazole once per day (n = 102) and 150 mg of ranitidine twice per day (n = 103) were 89.2% and 75.7%, respectively. The single daily dose of omeprazole worked significantly better than the doses of ranitidine (p < 0.001). The omeprazole group, in comparison to the ranitidine group, had a significantly higher number of patients without symptoms (37.8% vs 54.7%) and a lesser percentage of moderate symptoms (9.45% vs 19.8%). CONCLUSIONS Maintenance treatment with omeprazole (20 mg once daily) is superior to ranitidine (150 mg twice daily) in keeping patients with mild to moderate erosive reflux esophagitis in remission over a 6-month period.