Control of esophageal acid exposure is important in treating patients with gastroesophageal reflux disease (GERD). After complete healing of esophagitis, most patients will relapse within 6 months if left untreated. This multicenter, randomized, double-masked, placebo-controlled trial, conducted in the United States, examined whether two famotidine dosing regimens are effective in extending the time in remission for patients with moderate-to-severe erosive esophagitis. Of 172 patients enrolled, 31 received placebo, 69 received famotidine 20 mg twice daily (BID) , and 72 received famotidine 40 mg BID. Endoscopy was scheduled at baseline and at months 3 and 6. Patients assessed global heartburn and symptom relief at months 3 and 6 relative to the start of the study. Life table (Kaplan-Meier) relapse rates at 6 months were 22% (P < 0.001 vs placebo) for famotidine 20 mg BID, 11% (P < 0.001 vs placebo) for famotidine 40 mg BID, and 62% for placebo. Compared with placebo, patients in the famotidine groups were significantly less likely to note global symptomatic deterioration, as measured by the distribution of global assessment responses. The incidence of clinical and laboratory adverse experiences was similar among treatment groups. For maintenance treatment of GERD, famotidine 20 mg BID and 40 mg BID are more effective than placebo in extending the time in remission.