We investigated how often Helicobacter pylori was resistant to metronidazole before treatment in 283 H. pylori positive patients and whether the in vitro susceptibility to metronidazole could predict the clinical outcome of several drug regimens containing metronidazole. Metronidazole susceptibility was tested using either disc diffusion or plates containing metronidazole. Metronidazole-resistant strains were found in 41% of patients before their first anti-H. pylori treatment course. In patients with metronidazole-susceptible isolates, eradication was achieved in 74% after colloidal bismuth subcitrate (CBS) with metronidazole and in 91% after triple therapies consisting of CBS, metronidazole and amoxicillin or tetracycline. Dual therapies of 1 or 4 weeks' duration and triple therapies lasting 1 week were ineffective in patients with metronidazole-resistant strains. A 4-week course of triple therapy could still eradicate H. pylori in 68% of patients with metronidazole-resistant strains, but at the cost of significant side-effects. It is concluded that metronidazole resistance is common and is generally associated with a poor outcome of anti-H. pylori therapies containing metronidazole. Alternative drug schedules are urgently needed for patients with metronidazole-resistant H. pylori.