Therapy for Helicobacter pylori, the causative agent in more than 90% of peptic ulcer disease, is becoming more difficult because of increased resistance to antibiotics commonly used for treatment. Osato et al analyzed data from 17 US-based clinical trials to establish the rate of resistance to metronidazole, clarithromycin, and amoxicillin, and to assess whether there is an increase in resistance in certain demographic areas. Based on agar dilution procedures, resistance to clarithromycin and metronidazole increased modestly between 1993 and 1999. Amoxicillin resistance was rare, occurring in only 2 patients. Women were more apt to have metronidazole- or clarithromycin-resistant H pylori than men. Subjects who were older than 70 years of age had a significantly lower prevalence of resistant isolates than other subjects. No demographic differences were detected. Test method affected the results of susceptibility testing for metronidazole resistance rates but not for clarithromycin resistance rates.