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Introduction: Sickle cell disease mainly affects African Americans, and studies on racial differences in sickle cell disease outcomes are scanty. This study examined racial and ethnic differences in sickle cell disease prevalence, comorbidities, and outcomes. Methods: Using the National Inpatient Sample database from 2016 to 2018, we identified patients' records with a diagnosis of sickle cell disease using the International Classification of Diseases, Tenth Revision codes. The overall study population was further stratified by race into Blacks, Whites, and Hispanics. Using logistic regression, comorbidities and outcomes among sickle cell disease patients were compared between the three races/ethnicities. Results: Of the 74 817 hospitalized for sickle cell disease, 69 889 (93.4%) were Blacks, 3603 (4.8%) were Hispanics, and 1325 (1.8%) were Whites. Compared to Whites, Blacks were more likely to have significantly higher odds of sickle cell crisis