OBJECTIVE The aim of this study was to examine whether smoking or consumption of alcohol or coffee is associated with active Helicobacter pylori (H. pylori) infection. METHODS This was a cross-sectional population study conducted as part of a randomized controlled trial of H. pylori infection eradication in southwest England. A total of 10,537 subjects, recruited from seven general practices, underwent 13C-urea breath testing for active infection with H. pylori and provided data on smoking, usual weekly consumption of alcohol, and daily intake of coffee. RESULTS Smoking or coffee consumption were not related to active H. pylori infection. Total alcohol consumption was associated with a small, but not statistically significant, decrease in the odds of infection. After adjustment for age, sex, ethnic status, childhood and adult social class, smoking, coffee consumption, and intake of alcoholic beverages other than wine, subjects drinking 3-6 units of wine/wk had an 11% lower risk of H. pylori infection compared with those who took no wine: OR = 0.89, 95% CI = 0.80-0.99. Higher wine consumption was associated with a further 6% reduction in the risk of infection: OR = 0.83, 95% CI = 0.64-1.07. Intake of 3-6 units of beer (but no greater intake) was associated with a similar reduction in the risk of infection when compared to no beer intake (OR = 0.83, 95% CI = 0.75-0.91). CONCLUSIONS This study indicates that modest consumption of wine and beer (approximately 7 units/wk) protects against H. pylori infection, presumably by facilitating eradication of the organism.