The highest H. pylori eradication rates have been reported with triple therapy, using metronidazole with amoxycillin or tetracycline, and colloidal bismuth subcitrate or bismuth subsalicylate. The use of such therapies, however, may be impeded by a number of major disadvantages, including reduced patient compliance, the incidence of adverse events and primary or acquired antibiotic resistance. Patient compliance is a particular problem with triple therapy owing to the quantity of drugs taken, treatment duration and regimen complexity; the eradication rate is reduced from 96% to 69% when only 60% of the medication is taken. The risk of adverse events resulting from the inclusion of antibiotics in the regimen is increased in triple therapy, and this generates reluctance in many practitioners to prescribe such therapy despite its well-documented efficacy. An important cause of antibiotic failure lies in the development of H. pylori resistance; between 6% and 27% of H. pylori strains are primarily resistant to the 5-nitroimidazoles--metronidazole and tinidazole--both of which are used in triple therapy. In contrast, no resistance of H. pylori to amoxycillin has been reported. The combination of an acid pump inhibitor with a single antibiotic represents a promising novel therapy for H. pylori-associated peptic ulcer disease. Treatment with omeprazole and amoxycillin could provide both rapid healing of ulcers and eradication of H. pylori, coupled with few adverse events, good drug compliance and low ulcer relapse rates, and may replace triple therapy as first-line medication.