BACKGROUND Gastro-oesophageal reflux disease has a chronic course, and often requires long-term treatment. Proton pump inhibitors are the treatment of choice for both acute and maintenance treatment, but little is known from randomized controlled trials of their effects beyond 1 year. OBJECTIVE To compare the efficacy and safety of two doses of rabeprazole with 20 mg omeprazole in the maintenance treatment of erosive gastro-oesophageal reflux disease over 5 years. METHODS Two hundred and forty-three patients who had previously responded to acute treatment for erosive gastro-oesophageal reflux disease were prospectively randomized to receive 5 years of treatment with rabeprazole (10 or 20 mg daily) or omeprazole (20 mg daily). The primary outcome measure was endoscopically confirmed relapse of erosive gastro-oesophageal reflux disease. RESULTS One hundred and twenty-three patients (51%) completed all 5 years of the study, with similar completion rates in the three groups. Relapses occurred in nine of 78 (11.5%), eight of 82 (9.8%) and 11 of 83 (13.3%) patients in the rabeprazole 20 mg, rabeprazole 10 mg and omeprazole 20 mg groups, respectively. Gastric biopsy showed no evidence of any harmful effects. All treatments were well tolerated. CONCLUSIONS Rabeprazole 10 mg, rabeprazole 20 mg and omeprazole 20 mg all had similar efficacy in the maintenance treatment of gastro-oesophageal reflux disease. All three were safe and well tolerated during 5 years of treatment.