Background Oral anticoagulation (OAC) therapy prevents morbidity and mortality in nonvalvular atrial fibrillation; whether location of diagnosis influences OAC uptake or adherence is unknown. Methods and Results Retrospective cohort study (2008-2019), identifying adults with incident nonvalvular atrial fibrillation across health care settings (emergency department, hospital, outpatient) at high risk of stroke. OAC uptake and adherence via proportion of days covered for direct OACs and time in therapeutic range for warfarin were measured. Proportion of days covered was categorized as low (0-39%), intermediate (40-79%), and high (80-100%). Warfarin control was defined as time in therapeutic range ≥65%. All-cause mortality was examined at a 3-year landmark. Among 75 389 patients with nonvalvular atrial fibrillation (47.0% women, mean 77.4 years), 19.7% were diagnosed in the emergency department, 59.1% in the hospital, and 21.2% in the outpatient setting. Ninety-day OAC uptake was 51.6% in the emergency department, 50.9% in the hospital, and 67.9% in the outpatient setting (<0.0001). High direct OAC adherence increased from 64.9% to 80.3% in the emergency department, 64.3% to 81.7% in the hospital, and 70.9% to 88.6% in the outpatient setting over time ( values for trend <0.0001). Warfarin control was 40.3% overall and remained unchanged. In multivariable analysis, outpatient diagnosis compared with the hospital was associated with greater OAC uptake (odds ratio [OR], 1.79; [95% CI, 1.72-1.87]) and direct OAC (OR, 1.42; [95% CI, 1.27-1.59]) and warfarin (OR, 1.49; [95% CI, 1.36-1.63]) adherence. Varying or persistently low adherence was associated with a poor prognosis, especially for warfarin. Conclusions Locale of nonvalvular atrial fibrillation diagnosis is associated with varying OAC uptake and adherence. Interventions specific to health care settings are needed to improve stroke prevention.