OBJECTIVE: To describe and explore the natural history of Helicobacter pylori infection and chronic gastritis in terms of gastric mucosal atrophy and ulcer development over time in a population-based cohort. MATERIAL AND METHODS: A population-based cohort of 314 volunteers was re-screened (median follow-up interval of 8.4 years) with gastroduodenoscopy with biopsy, assessment of H. pylori status, analysis of pepsinogens, and monitoring of a nonsteroidal anti-inflammatory drug (NSAID) use and alcohol and smoking habits. RESULTS: The incidence of duodenal or prepyloric ulcer was 0.45 per 100 person years and was associated with weekly NSAID use (odds ratios, OR 27.8), weekly alcohol consumption (OR 19.4) and smoking (OR 31.0), but not with H. pylori status. De novo infection with H. pylori was not observed, and the infection had disappeared in 11 of 113 subjects. Among subjects with chronic gastritis, the incidence of atrophy of the corpus mucosa was 1.4 per 100 person years. Atrophy development was related to age (OR 1.23) and to the severity of chronic inflammation in the corpus mucosa at baseline (OR 8.98). Substituting atrophy for subnormal S-pepsinogen I/S-pepsingen II gave similar results. CONCLUSIONS: In this cohort, the minimum incidence of ulcer was 0.45 per 100 person years. Smoking, alcohol, and NSAIDs, but not H. pylori infection were significant risk factors. The incidence of atrophy of the corpus mucosa was 1.4 per 100 person years with a positive relation to age and to the degree of chronic inflammation at baseline. Atrophy was stationary in advanced stages.