The use of vitamin K antagonists (VKAs), the cornerstone treatment for stroke prevention in patients with atrial fibrillation, is limited by the perceived risk of serious bleeding in Asia. Non-VKA oral anticoagulants (NOACs) are safer alternatives. Here, we evaluate performance differences of NOACs between Asians and non-Asians. We compared efficacy and safety of NOACs between patients enrolled in Asian and non-Asian countries using aggregative data from phase III clinical trials. The odds ratios (ORs 95% confidence interval) were calculated by a random effects model. Comparing with VKAs, standard-dose NOACs reduced stroke or systemic embolism (OR=0.65 0.52-0.83 versus 0.85 0.77-0.93, P interaction= 0.045) more in Asians than in non-Asians and were safer in Asians than in non-Asians about major bleeding (OR=0.57 0.44-0.74 versus 0.89 0.76-1.04, P interaction=0.004), hemorrhagic stroke (OR=0.32 0.19-0.52 versus 0.56 0.44-0.70, P interaction=0.046) in particular, whereas gastrointestinal bleeding was significantly increased in non-Asians (OR=0.79 0.48-1.32 versus 1.44 1.12-1.85, P interaction=0.041). Generally, low-dose NOACs were safer than VKAs without heterogeneity in efficacy and safety between Asians and non-Asians, except for ischemic stroke, major, and gastrointestinal bleeding. Our findings suggest that standard-dose NOACs were more effective and safer in Asians than in non-Asians, whereas low-dose NOACs performed similarly in both populations.