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There are data to suggest the existence of non–Helicobacter pylorigastritis. However, the risk factors and clinical course forH pylori–negative gastritis remain unclear. We aimed to examine the prevalence and determinants ofH pylori–negative gastritis in a large multiethnic clinical population.We conducted a cross-sectional study among patents scheduled for an elective esophagastroduodenoscopy or attending selected primary care clinics and eligible for screening colonoscopy at a single Veterans Affairs medical center. We identified cases ofH pylor–negative gastritis,H pylori–positive gastritis, andH pylori–negative nongastritis, where gastritis was defined by the presence of neutrophils and/or mononuclear cells. Risk factors forH pylori–negative gastritis were analyzed in logistic regression models.A total of 1240 patients had information from all biopsy sites, of whom 695 (56.0%) had gastritis.H pylori–negative gastritis was present in 123 patients (9.9% of all study subjects and 17.7% of all patients with gastritis). Among all patients with gastritis, African Americans were statistically significantly less likely than non-Hispanic whites to haveH pylori–negative gastritis (odds ratio, 0.25; 95% confidence interval, 0.14–0.43). Conversely, PPI users were more likely to haveH pylori–negative gastritis thanH pylori–positive gastritis compared with nonusers (odds ratio, 2.02; 95% confidence interval, 1.17–3.49). The cumulative incidence of gastric erosions and ulcers were higher in patients withH pylori–negative gastritis thanH pylori–negative nongastritis.We found thatH pylori–negative gastritis was present in approximately 18% of patients with gastritis. The potential forH pylori–negative gastritis to progress or the risk of gastric cancer of those with gastric mucosal atrophy/intestinal metaplasia remains unclear.