Eradication of Helicobacter pylori from the stomach by triple therapy with bismuth, tetracycline, and metronidazole cures peptic ulcer disease. We investigated whether concomitant acid inhibition with omeprazole would improve the results of triple therapy. 108 consecutive patients with peptic-ulcer disease and biopsy-proven H pylori infection were randomised to 7 days of triple therapy with or without omeprazole 20 mg twice daily. Patients in the omeprazole-treated group were pretreated with 3 days of omeprazole. Eradication of H pylori was assessed by 10 endoscopic biopsies for urease test, histology, and culture 4-6 weeks after treatment. 53 of 54 (98.1%) patients treated with omeprazole were cured compared with 45 of 54 (83.3%) of those not treated (p = 0.02), a difference in efficacy of 14.8% (95% Cl 4.2-25.4%). Most side effects were mild and did not interfere with compliance; 105 patients (97.2%) finished treatment. Gastro-intestinal side effects were significantly fewer in the omeprazole group. We conclude that the addition of omeprazole to triple therapy improves efficacy, lessens side effects, and is sufficiently efficacious to obviate the need for a diagnostic test of cure in compliant patients.