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Background A leading infectious cause of hospitalization among adults in the United States is community-acquired pneumonia (CAP). The etiology and incidence of CAP in American Indians/Alaskan Natives (AI/AN) has not been described. Methods We conducted a retrospective study by reviewing the medical records of all AI/AN patients 18 years or older admitted to W.W. Hastings Hospital in Tahlequah, Oklahoma with a diagnosis of a respiratory infection from January 1, 2016 to December 31, 2016. Only patients with a radiographically confirmed CAP were included and those with a recent hospitalization or immunosuppressed were excluded. Patient demographics, comorbidities and results of molecular tests, antigen detection, high quality sputum culture and blood culture were reviewed. Population-based incidence rates of CAP requiring hospitalization were calculated according to age. Results From January 2016 through December 2016, 763 patients were admitted with a diagnosis of a respiratory infection, of which 193 (25%) met the inclusion criteria. Of this group, 103 (53%) had at least one pathogen detected: one or more viruses were detected in 47 (24%), one or more bacteria were detected in 63 (33%). The most common pathogens were Streptococcus pneumoniae (12% of patients), rhinovirus/enterovirus (11% of patients), respiratory syncytial virus (5% of patients), legionella pneumophila (4% of patients), and human metapneumovirus (4% of patients). The annual incidence of CAP was 13.6 cases (95% confidence interval, 11.9, 15.7) per 10,000 adults, with the highest incidence among adults ages 65–79 (43 cases per 10,000 adults) and those 80 years of age or older (102 cases per 10,000 adults). Seventy-five percent of patients had an underlying medical condition, 47% had diabetes mellitus (DM), followed by chronic obstructive lung disease (38%) and chronic heart disease (32%). Conclusion In this AI/AN population, a respiratory pathogen was identified in 53% of the cases despite the use of cutting edge diagnostic tests in most patients. Bacteria were detected more often than viruses. Compared with recent publications of CAP affecting non-Hispanic whites, non-Hispanic blacks and Hispanics, the population described in this study was older and had higher prevalence of DM. Disclosures All authors: No reported disclosures.