BACKGROUND: Antimicrobial resistance of Helicobacter pylori is considered as the main cause of failure of eradication therapy. Because resistance to metronidazole has been reported in 25.8% to 66.2% of H. pylori, a combination of proton pump inhibitors (PPI), amoxicillin, and clarithromycin is currently recommended as a primary therapy. We investigated the prevalence of antimicrobial resistance to the primary drugs and the impact of antimicrobial resistance on eradication rates. METHODS: Between May and August 2005, H. pylori isolates from 93 patients were tested for antimicrobial susceptibility at Asan Medical Center. Susceptibility tests of clarithromycin and amoxicillin were performed by the disk diffusion method and those of metronidazole and tetracycline by Etest (AB Biodisk, Solna, Sweden). The medical records of the patients were reviewed to collect the data such as demographic findings, previous and current eradication therapies, and bacteriological outcome. The appropriate therapy was defined as three-drug-combination including susceptible drugs only, or four-drug-combination including metronidazole in the case of metronidazole-resistance. RESULTS: Resistance rates to clarithromycin and metronidazole were 17.2% and 33.3%, respectively, but there was no resistance to tetracycline and amoxicillin. The eradication was successful in 32 of the 36 patients (88.9%) who received the appropriate therapy, but none of 4 patients who received an inappropriate therapy (P<0.01). CONCLUSIONS: Resistance to clarithromycin seemed to increase and contribute to the failure of eradication therapy. For the appropriate therapy of H. pylori infection, the susceptibility results should be reported before initiation of the eradication therapy.