In clinical practice, eradication of Helicobacter pylori infection may be difficult due to medication side effects and the need for 2 weeks of therapy. Because therapies of shorter duration may improve patient compliance and reduce treatment side effects, we compared the efficacy and tolerability of two anti-H. pylori treatments of 1 week's duration. Patients with H. pylori infection were randomized to treatment with either (a) short-course triple therapy, composed-of bismuth subsalicylate (Pepto-Bismol, Procter & Gamble, Cincinnati, OH, U.S.A.) two tablets four times daily, amoxicillin 1 g (two 500-mg tablets) twice daily, and metronidazole 500 mg four times daily on days 5-7 or (b) omeprazole 40 mg twice a day with amoxicillin 1 g twice a day for 1 week. At least 4 weeks posttreatment, efficacy was evaluated with either histological evaluation of antral biopsies for H. pylori or 14C urea breath testing. Patients who failed initial therapy were allowed to cross over to the alternative treatment regimen after a minimum "wash-out" period of 5 weeks. Patients completed a diary during therapy to monitor both compliance and side effects. Thirty-four patients completed the study, 10 receiving both treatment regimens. Treatment with the shortcourse triple therapy eradicated H. pylori in 78.3% of treatments compared with 38% with the high-dose omeprazole/ amoxicillin combination (p < 0.05). Patients were highly compliant with both treatments, and mild side effects, such as transient loose stools or abdominal pain, were common in both groups. This is the first report from North America confirming the success of the short-course triple therapy for the eradication of H. pylori. The high-dose omeprazole/ amoxicillin regimen's eradication rate was markedly inferior to that achieved by the short-course triple therapy regimen and should not be used. Comparative studies of the short-course triple therapy regimen with other 7-day anti-H. pylori treatment regimen therapies are indicated.