INTRODUCTION: The prevalence of Helicobacter pylori has been declining overall, but there is no current screening strategy in the U.S. to identify patients with H. pylori. We identified the prevalence and predictors of H. pylori infection among patients undergoing upper endoscopy with gastric biopsies in the Harris County Hospital System. METHODS: We identified consecutive patients undergoing upper endoscopy with gastric biopsies for any indication from two hospitals in the Harris County Hospital System in Houston, TX during 1/2015-12/2016. We abstracted sociodemographic, laboratory, endoscopic, and histopathologic data from the medical record to evaluate previous as well as active H. pylori infection seen on gastric biopsy. We determined the overall and race/ethnic specific prevalence of H. pylori infection. We evaluated associations between demographic, lifestyle, and endoscopic features with H. pylori infection in logistic regression models, reported as odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Of 943 patients who underwent gastric biopsies, 376 were men (39.9%) with mean age 53.0 years (SD 11.6 years). Most were Hispanics (51.1%) or blacks (26.0%) with a small proportion of whites (11.1%). The overall prevalence of H. pylori infection was 52.8% (n = 498), which was highest among Hispanics (60.2%), blacks (51.0%), and Asians (52.3%) compared to whites (21.9%). Of 943 patients, 486 (51.5%) were previously screened for H. pylori infection, and 301 (31.9%) had tested positive. Predictors of H. pylori included male sex (adjOR 1.53, 95% CI 1.10-2.13), race (vs. white, black adjOR 3.76, 95% CI 2.19-6.45; Hispanic adjOR 5.31, 95% CI 3.14-9.00; Asian adjOR 3.96, 95% CI 1.93-8.11), and proton pump inhibitor use (adjOR 1.50, 95% CI 1.10-2.05). Gastric polyps identified on endoscopy were associated with the absence of H. pylori (OR 0.57, 95% CI 0.37-0.88). There were no significant associations with age, family history of gastric cancer, smoking, alcohol use, or endoscopy indication. CONCLUSION: In this contemporary U.S. cohort of patients undergoing endoscopy with gastric biopsies, the overall prevalence of H. pylori infection is very high (52.8%). Black, Hispanic, and Asian race were associated with high H. pylori infection, and men were at higher risk of developing this infection. These findings call for developing a H. pylori screening strategy in certain high risk U.S. populations.