BACKGROUND We investigated the risk relationship between histotopographic patterns of Helicobacter pylori gastritis and peptic ulcer site. METHODS Three hundred and eighty-three infected patients were classified as having duodenal ulcer (n = 79), prepyloric ulcer (n = 39), gastric (angular) ulcer (n = 28), and no ulcer (n = 237). Antral and corpus biopsy specimens were taken. Sydney system-based scores for bacterial density and activity and degree of gastritis were added to antral and corpus sum scores (SS) (range, 0-9). These were used to categorize the phenotype of gastritis. In addition, the presence or absence of mucosal atrophy was taken into account. The relative risk for ulcer association with these conditions was calculated. RESULTS High-grade antral (SS > 5) associated with mild to moderate corpus (SS > 5) gastritis increased duodenal (RR = 4.9; confidence interval (CI), 2.8-8.5) and prepyloric ulcer risk (RR = 2.99; CI, 1.4-6.2). High-grade gastritis in the antrum (SS > 5) and corpus (SS > 5) increased gastric ulcer risk (RR = 3.7; CI, 1.6-8.3). Antral atrophy and/or intestinal metaplasia is associated with an increased gastric ulcer risk (RR = 3.3; CI, 1.4-7.8). CONCLUSIONS The pattern of H. pylori gastritis may define a risk for peptic ulcer at various sites, but additional factors, not reflected in histology, also contribute to this risk.