Background & Aims Nearly all studies of gastric adenocarcinoma in the United States have relied on national cancer databases, which do not include data on Helicobacter pylori infection, the most well-known risk factor for gastric cancer. We collected data from a large cohort of patients in the United States to calculate the incidence of and risk factors for nonproximal gastric adenocarcinomas after detection of H pylori. Secondary aims included identifying how treatment and eradication affect cancer risk. Methods We performed a retrospective cohort study, collecting data from the Veterans Health Administration on 371,813 patients (median age 62 years; 92.3% male) who received a diagnosis of H pylori infection from January 1, 1994, through December 31, 2018. The primary outcome was a diagnosis of distal gastric adenocarcinoma 30 days or more after detection of H pylori infection. We performed a time to event with competing risk analysis (with death before cancer as a competing risk). Results The cumulative incidence of cancer at 5, 10, and 20 years after detection of H pylori infection was 0.37%, 0.5%, and 0.65%, respectively. Factors associated with cancer included older age at time of detection of H pylori infection (subhazard ratio [SHR], 1.13; 95% confidence interval [CI], 1.11–1.15; P Conclusions In a study of 371,813 veterans with a diagnosis of H pylori infection, we found significantly higher risks of gastric cancer in racial and ethnic minorities and smokers. Treatment of H pylori infection decreased risk only if eradication was successful. Studies are needed on the effects of screening high-risk persons and to identify quality measures for diagnosis, resistance patterns, and treatment efficacy.