The objective of this study was to compare the risk of stroke in atrial fibrillation (AF) with adherent use of oral anticoagulation (OAC), non-adherent use, and non-use of OAC.Using 2013-2016 Medicare claims data, we identified patients newly diagnosed with AF in 2014-2015 and collected prescriptions filled for OAC in the 12 months after AF diagnosis (n = 39,272). We categorized participants each day into three time-dependent exposures: adherent use (≥ 80% of the previous 30 days covered with OAC), non-adherent use (0-80% covered with OAC), and non-use (0%). We constructed Cox proportional hazards models to estimate the association between time-dependent exposures and time to stroke, adjusting for demographics and clinical characteristics.The sample included 39,272 patients. Study participants spent 35.0% of the follow-up period in the adherent use exposure category, 10.9% in the non-adherent category, and 54.0% in the non-use category. OAC adherent use [hazard ratio (HR) 0.62; 95% confidence interval (CI) 0.52-0.74] and non-adherent use (HR 0.74; 95% CI 0.57-0.95) were associated with lower hazards of stroke than non-use. Adherent use of DOAC (HR 0.54; 95% CI 0.42-0.69) and warfarin (HR 0.70; 95% CI 0.56-0.89) was associated with lower risk of stroke than non-use, but the risk of stroke did not statistically differ between DOAC and warfarin adherent use (HR 0.77; 95% CI 0.56-1.04).Although adherence to OAC reduces stroke risk by nearly 40%, newly diagnosed AF patients in Medicare adhere to OAC on average only one third of the first year after AF diagnosis.