Background and Purpose-Ischemic stroke (IS) secondary to atrial fibrillation (AF) is largely preventable with the use of anticoagulation. We sought to identify race-ethnic and sex disparities with the use of direct oral anticoagulants (DOACs), aspirin, and warfarin in IS patients with AF, and to identify temporal trends in the utilization of these medications. Methods: The FLorida PuErto Rico Atrial Fibrillation (FLiPER-AF) Stroke Study included 24,040 IS cases enrolled in the Florida-Puerto Rico Collaboration to Reduce Stroke Registry (CReSD) from 2010 to 2016. Multivariable logistic regression models were performed to evaluate the effect of race-ethnicity and sex on utilization of DOACs, aspirin and warfarin for stroke prevention in AF after adjustment for sociodemographic, hospital and clinical factors. Results: Among 24,040 IS cases, 54% were women and 10% Black, 12% FL-Hispanics, 4% PR-Hispanic and 74% Whites. From 2010 to 2016, DOAC use increased from 0% to 36%, warfarin use decreased from 51% to 17% and aspirin use remained relatively stable (42% to 40%). After adjustment, Blacks had higher odds of warfarin (OR=1.22, 95% CI 1.07-1.40) prescription at discharge compared to Whites. Men had higher rates of aspirin (42.1% vs 38.8%), warfarin (33.6% vs. 28.9%) and DOAC (21.3% vs. 19.3%) use compared to women. After adjustment, women had lower odds of being discharged on aspirin (OR=0.92, 95% CI 0.86-0.98) or warfarin (OR=0.91, 95% CI 0.84-0.99). There was no sex difference in use of DOACs. Conclusions: Our study confirmed the increasing use of DOACs, down-trending use of warfarin, while aspirin use remained similar over the years. There are gender and race-ethnic disparities in anticoagulation use in IS patients with AF. It is critical to understand underlying drivers of these disparities in order to develop better practice strategies for stroke prevention in patients with AF.