Background and Purpose- Limited evidence exists on the effectiveness and safety of warfarin and all 4 available non-vitamin K antagonist oral anticoagulants (NOACs) from current clinical practice in the Asian population with nonvalvular atrial fibrillation. We aimed to evaluate the comparative effectiveness and safety of warfarin and 4 NOACs. Methods- We studied a retrospective nonrandomized observational cohort of oral anticoagulant naïve nonvalvular patients with atrial fibrillation treated with warfarin or NOACs (rivaroxaban, dabigatran, apixaban, or edoxaban) from January 2015 to December 2017, based on the Korean Health Insurance Review and Assessment database. For the comparisons, warfarin to 4 NOACs and NOAC to NOAC comparison cohorts were balanced using the inverse probability of treatment weighting. Ischemic stroke, intracranial hemorrhage, gastrointestinal bleeding, major bleeding, and a composite clinical outcome were evaluated. Results- A total of 116 804 patients were included (25 420 with warfarin, 35 965 with rivaroxaban, 17 745 with dabigatran, 22 177 with apixaban, and 15 496 with edoxaban). Compared with warfarin, all NOACs were associated with lower risks of ischemic stroke, intracranial hemorrhage, gastrointestinal bleeding, major bleeding, and composite outcome. Apixaban and edoxaban showed a lower rate of ischemic stroke compared with rivaroxaban and dabigatran. Apixaban, dabigatran, and edoxaban had a lower rate of gastrointestinal bleeding and major bleeding compared with rivaroxaban. The composite clinical outcome was nonsignificantly different for apixaban versus edoxaban. Conclusions- In this large contemporary nonrandomized Asian cohort, all 4 NOACs were associated with lower rates of ischemic stroke and major bleeding compared with warfarin. Differences in clinical outcomes between NOACs may give useful guidance for physicians to choose drugs to fit their particular patient clinical profile.