Objective <p>Rheumatic heart disease (RHD) is the most common acquired heart disease in children in the USA and worldwide. This study compares the diagnosis and outcomes of Indigenous and non-Indigenous youth with acute rheumatic fever (ARF) and RHD at a US children’s hospital serving a several state catchment area with a large Indigenous population (&gt;270 tribes representing 9.2% of the total US Indigenous population).</p> Methods <p>This study involved a retrospective analysis of patients presenting to a major children’s hospital between 2008 and 2018. Individuals aged 4–17 with a diagnosis of ARF or RHD were identified using International Classification of Diseases, Ninth and Tenth Revision (ICD-9, 10) codes. Patients with congenital heart disease were excluded.</p> Results <p>Chart review was performed on 132 individuals with ARF/RHD. 61% of individuals with non-missing race identified as Indigenous (defined as American Indian, Alaska Native, Native Hawaiian, or Pacific Islander). Average age at diagnosis was found to be 10.3 years for Indigenous youth, compared to 9.1 years for non-Indigenous youth. Indigenous youth were more likely to have cardiac involvement at the time of diagnosis. Indigenous youth had higher rates of aortic regurgitation on initial echocardiography, but no other significant differences were found in incidence of echocardiographic findings.</p> Conclusion <p>Indigenous youth were diagnosed with rheumatic fever at a later age than non-Indigenous youth, and more likely to have cardiac involvement at time of diagnosis, indicating disparities between the two populations. This suggests a need for further study and development of screening tools.</p>