BACKGROUND: Stroke associated with atrial fibrillation (AF) is a significant cause of mortality. This study analyzed demographic trends and disparities in mortality rates due to stroke in AF patients aged ≥25 years. METHODS: A retrospective analysis was conducted to acquire death data using the Centers for Disease Control and Prevention database from 1999 to 2020. Age-adjusted mortality rates (AAMRs) were calculated per 100,000 persons, and trends were assessed using Average Annual Percentage Change (AAPC) and annual percent change (APC). Data were stratified by year, sex, race/ethnicity, and geographical regions. RESULTS: Between 1999 and 2020, AF-associated stroke contributed to 331,106 deaths among adults in this study population. Deaths occurred predominantly in medical facilities (43.2 %). The overall AAMR for AF-associated stroke decreased from 7.4 in 1999 to 6.4 in 2020, with an APC of -1.02 ( CONCLUSION: This analysis depicts significant demographic and geographic disparities in mortality rates attributed to stroke associated with AF. Targeted interventions and equitable healthcare access are crucial to mitigate these disparities and improve outcomes for this population.