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Background Native Americans are overrepresented in outbreaks of Group A Streptococcus (GAS) in the United States (US). In 2016, several invasive cases of GAS were detected at the Whiteriver Indian Health Service (IHS) Hospital in Arizona that primarily serves the White Mountain Apache (WMA) Tribe. The objective of this study was to determine the burden of invasive and severe GAS disease among Native Americans on the WMA Tribal lands. Methods Prospective population and laboratory-based surveillance for invasive and severe GASinfections was conducted for two years from March 2017 through February 2019. A case was defined as a Native American individual living on or around WMA Tribal lands with GAS isolated from a normally sterile body site (invasive) or from a non-sterile site (e.g. wound, throat, ear) requiring hospitalization (severe). Incidence rates were calculated using the IHS User Population as the denominators. Age-standardized incidence rates were calculated using US Census data from 2015 as the reference group. Results 157 cases were identified (Year 1: 85; Year 2: 72), including 42 (27%) invasive and 115 (73%) severe cases. Most cases were adults (88.5%; median age: 40.5 years) and had ≥1 underlying medical condition (99.4%), including alcoholism (57.1%), hypertension (37.2%), and diabetes (34.0%). 47.8% of cases had a trigger in the past two weeks, including penetrating trauma (31.8%) and blunt force trauma (14.0%). For 72.9% of cases, a co-infection was detected (most commonly Staphylocccus aureus : 96.8%). 4.5% of cases required amputation and 1.9% died within 30 days of initial culture. The incidence of invasive and severe GAS was 460.9 per 100,000 persons (95% confidence interval: 394.3, 538.8), with no significant difference by year. The incidence was highest among adults ≥65 and lowest among children 5–17 years of age. Age-standardized incidence rates of invasive and severe GAS and invasive only GAS are presented in the Figure. Conclusion The WMA community has experienced disproportionately high rates of invasive and severe GAS for over two years. Studies to determine the reservoirs for transmission are urgently needed, as are interventions to reduce the morbidity and mortality associated with these infections. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]