OBJECTIVE: To measure the prevalence of metronidazole- or clarithromycin-resistant Helicobacter pylori. DESIGN. Retrospective. METHOD: All positive H. pylori cultures with known susceptibility to metronidazole or clarithromycin between 1998 and 2003 were selected from the database of the Microbiology Laboratory in 's-Hertogenbosch, the Netherlands. Resistance to clarithromycin and metronidazole was determined using the E-test with cut-off minimum inhibitory concentrations of > or = 2 microg/ml and > or = 8 microg/ml, respectively. RESULTS: Of the 960 cultures with known metronidazole susceptibility, 135 (14%) were resistant. Of the 959 cultures with known clarithromycin susceptibility, 26 (3%) were resistant. The percentages of resistant cultures were higher in women than in men (17% versus 12% and 4% versus 2%, respectively). There was no relationship between age and resistance. Over the course of the study period, resistance to metronidazole decreased slightly, whereas resistance to clarithromycin increased slightly. CONCLUSION: Prevalence of metronidazole- and clarithromycin-resistant H. pylori strains in the 's-Hertogenbosch region was so low that the combination of a proton pump inhibitor, clarithromycin and amoxicillin can be used in patients with H. pylori infection without first determining susceptibility.