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To describe the epidemiology of ulcers, gastric cancer, and Helicobacter pylori infection among American Indian (AI) and Alaska Native (AN) persons, we analyzed hospitalization discharge records with physician discharge diagnoses coded as ulcer, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma during 1980 to 2005, and H. pylori during 1996 to 2005 from the Indian Health Service Inpatient Dataset. The average annual age-adjusted rate of hospitalizations that included an ulcer-associated condition was 232.4 per 100,000 AI/AN persons. The age-adjusted rate for gastric cancer was 14.2 per 100,000 persons. MALT lymphoma was listed as a discharge diagnosis at an age-adjusted rate of 6.1 per 100,000, and the age-adjusted rate of H. pylori discharge diagnoses was 28.2 per 100,000. The AI/AN persons living in the Alaska region and those ≥ 65 years old had the highest rates of hospitalizations that listed ulcer-associated conditions, gastric cancers, MALT lymphoma, and H. pylori as a discharge diagnosis.