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BACKGROUND It is unclear whether edoxaban shows better risk reduction of ischemic stroke, bleeding, and all-cause mortality than warfarin in Asian patients with nonvalvular atrial fibrillation (AF). OBJECTIVES This study compared the effectiveness and safety of edoxaban with those of warfarin in a Korean population with AF. METHODS Using the Korean National Health Insurance Service database, we included new users of edoxaban and warfarin in patients with AF from January 2014 to December 2016 (n = 4,200 on edoxaban, and n = 31,565 on warfarin) and analyzed the risk of ischemic stroke, intracranial hemorrhage (ICH), hospitalization for gastrointestinal (GI) bleeding, hospitalization for major bleeding, and all-cause death. The propensity score matching method was used to balance covariates across edoxaban and warfarin users. RESULTS We compared a 1:3 propensity score-matched cohort of patients with AF who were new users of edoxaban and warfarin (n = 4,061 and n = 12,183, respectively). Baseline characteristics were balanced between the 2 groups (median age 72 years; median CHA2DS2-VASc [congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke, transient ischemic attack, or thromboembolism, vascular disease, age 65-74 years, sex category (female)] score 3). Edoxaban users had a significantly lower risk of ischemic stroke (hazard ratio [HR]: 0.693; 95% confidence interval [CI]: 0.487 to 0.959), ICH (HR: 0.407; 95% CI: 0.182 to 0.785), hospitalization for GI bleeding (HR: 0.597; 95% CI: 0.363 to 0.930), hospitalization for major bleeding (HR: 0.532; 95% CI: 0.352 to 0.773), and all-cause death (HR: 0.716; 95% CI: 0.549 to 0.918) than warfarin users. All subgroups (age, sex, CHA2DS2-VASc score, renal function, edoxaban dose) showed better clinical outcomes with edoxaban than with warfarin. CONCLUSIONS In this real-world Asian population with AF, edoxaban might be associated with reduced risk of ischemic stroke, major bleeding, and all-cause death compared with warfarin. These benefits were consistent across various high-risk subgroups.