OBJECTIVE: To compare the efficacy of the prokinetic drug cisapride and the antisecretory agent ranitidine in relieving symptoms of functional dyspepsia, as well as their effect on the recurrence of symptoms after the discontinuation of treatment. DESIGN: A randomized double-blind parallel-group trial of cisapride 30 mg daily and ranitidine 300 mg daily given for 2, 4 or 8 weeks, followed by a 4-week drug-free follow-up of the patients with a good or excellent response. Rescue antacid tablets were allowed only if pain was unbearable. PATIENTS: A total of 203 patients (99 cisapride, 104 ranitidine) with symptoms of functional dyspepsia for more than 4 weeks, after the exclusion of organic disease by endoscopy and sonography or radiology. RESULTS: Cisapride and ranitidine improved the symptoms of diffuse epigastric pain, postprandial epigastric fullness, epigastric distension, belching, heartburn, regurgitation, and nausea when compared with baseline. Pain at night and gastric discomfort also greatly improved. Cisapride produced a greater reduction in epigastric pain (P = 0.07) and epigastric distension (P = 0.03) scores than ranitidine. Both drugs were equally effective in reducing the concomitant reflux-like symptoms of heartburn and regurgitation. At week 8, 87% of cisapride patients versus 61% of ranitidine patients had an excellent or good result. The deterioration of symptoms during the follow-up phase was limited in both groups. However, after the withdrawal of medication there was a greater reduction in scores in the cisapride group than in the ranitidine group for diffuse epigastric pain (P = 0.05), epigastric distension (P = 0.002), the cluster of six symptoms of epigastric discomfort (P = 0.05), and the cluster of all nine upper gastrointestinal symptoms (P = 0.06). Adverse events occurred in 15 cisapride patients and 18 ranitidine patients, and two of the ranitidine patients were withdrawn from treatment. CONCLUSIONS: Although cisapride and ranitidine both improved the symptoms of functional dyspepsia, cisapride was superior to ranitidine, particularly on the combined evaluation of the response to treatment and the recurrence of symptoms.