ABSTRACT: Non-vitamin K antagonist oral anticoagulants such as edoxaban are the standard of care for stroke prevention in patients with atrial fibrillation (AF). The Global Edoxaban Treatment in routiNe clinical prActice (ETNA)-AF program integrates prospective, observational, noninterventional regional studies from Europe, Japan, and other Asian countries, collecting data on patient characteristics and clinical outcomes in unselected patients treated with edoxaban for stroke prevention in AF. Overall, 26,823 patients completed a 1-year follow-up and were treated with edoxaban; either 60 or 30 mg once daily. The majority (82.6%) of patients received the recommended doses according to the local label. At baseline, the median (interquartile range) age was 75 (68, 80) years, the CHA2DS2-VASc score was 3.0 (2.0, 4.0), and the hypertension, abnormal renal and liver function, stroke, bleeding, labile international normalized ratio, elderly, drugs, or alcohol (HAS-BLED) score was 2.0 (2.0, 3.0). At one year, there were 273 (1.12%/year) major bleeding events, including 75 (0.31%/year) intracranial hemorrhages and 140 (0.57%/year) major gastrointestinal (GI) bleeds. There were 214 ischemic strokes (0.87%/year). Mortality was 3.03%/year (745 deaths), and cardiovascular mortality accounted for 40% of all deaths (1.22%/year, 299 cardiovascular deaths). In conclusion, stroke, intracranial hemorrhage, and other major bleeding events were low in patients with AF treated with edoxaban in routine care. Even on anticoagulation, cardiovascular death remained common.