During 1998-2004, a total of 218 Helicobacter pylori isolates were obtained from patients who were randomised to receive one of the following regimens in a medical centre in Taiwan: lansoprazole, amoxicillin and clarithromycin (LAC) therapy; or lansoprazole, metronidazole and clarithromycin (LMC) therapy. In the LMC group, resistance rates for metronidazole and clarithromycin reduced from 48.6% (1998-2000) to 20.4% (2001-2004) (P<0.05) and from 13.5% to 6.3% (P<0.05), respectively. Analysis of annual antimicrobial consumption found that metronidazole use was slowly decreased both in the total population and in gastrointestinal disease patients. The per-protocol analysis revealed a higher eradication rate for patients using LMC therapy in 2001-2004 (82.6% vs. 75.0%), whilst there was similar efficacy for LAC therapy (84.8% vs. 84.2%). This observation suggests an effective programme to control H. pylori antibiotic resistance and hence elevate its cure rate.