Abstract Body: Introduction:Stroke is the second leading cause of death worldwide,around 50,000 U.S. residents with valvular heart disease experiencing a stroke annually. This study examines trends in stroke-related mortality due to mitral valve disorders (MVD) in the U.S. from 1999 to 2020, with a focus on demographic factors and racial disparities.The goal is to inform public health strategies and improve prevention and treatment efforts. Methods:We analyzed death certificate data from the CDC's WONDER database from 1999 to 2020, focusing on stroke and MVD-related mortality (ICD-10 code I64.0 “Stroke” and Code I34.0 “MVD”) in adults aged ≥25 years. Using joint point regression analysis, we calculated annual percent changes (APCs) in age-adjusted mortality rates (AAMRs) with 95% confidence intervals across various demographic (sex,race/ethnicity,age) subgroups.Results:The AAMR for stroke due to MVD-related mortality decreased in the US from an adjusted rate (AR) 98.6 in 1999 to 92.9 in 2001 (APC: -2.64%; 95% CI: -4.18% to -1.35%),after which it decreased to 59.6 in 2009 (APC: -5.47%; 95% CI: -6.20% to -5.19%) then it further reduced to 50.1 in 2015 (APC: -2.84%; 95% CI: -3.27% to -1.78%).The AAMR decreased in 2018 to 40.2 (APC: -7.28%; 95% CI: -8.08% to -6.22%) after which it increased to 43.9 in 2020 (APC: 4.15%; 95% CI: 2.56% to 5.59%). Males had higher consistently higher AAMRs than females (47.8 vs. 40.3).The AAMR in the US men decreased from 103.6 in 1999 to 51.5 in 2015 (APC: -2.62%; 95% CI: -3.04% to -1.49%) after which it decreased further to 42.2 in 2018 (APC: -6.75%; 95% CI: -7.72% to -5.48%) & then it increased to 47.8 in 2020 (APC: 6.11%; 95% CI: 4.10% to 7.85%).The AAMR in the US women decreased from 94.1 in 1999 to 48.3 in 2015 (APC: -3.05%; 95% CI: -3.51% to -1.75%) after which it decreased further to 38.2 in 2018 (APC: -7.57%; 95% CI: -8.81% to -6.18%) and then it increased to 40.3 in 2020 (APC: 2.32%; 95% CI: -0.26% to 4.49%).The non-Hispanic (NH) Black or African American (AA) has the greatest AAMR (69.2), followed by the NH American Indian or Alaska Native with an AAMR (44.2) and the NH White population with an AAMR (42.4).The low-risk populations were the Hispanic or Latino (33.6) and the NH Asian or Pacific Islander(31).Conclusions:The mortality rates from stroke due to MVD have overall increased in the United States over the past two decades, specifically men & (NH) Black or AA, NH American Indian or Alaska Native, and (NH) White are at high risk.