Abstract Aims Prior studies suggested that the risks of ischaemic stroke and bleeding in patients of Asian race with atrial fibrillation (AF) may be higher than that of non-Asians. In the analysis of ENGAGE AF-TIMI 48 trial, we compared clinical outcomes, edoxaban concentration, and anti-factor Xa (anti-FXa) activity, between Asian and non-Asian races. Methods and results There were 2909 patients of Asian race and 18 195 non-Asian race in the ENGAGE AF-TIMI 48 trial. The risks of thromboembolism and bleeding events were compared for Asians and non-Asians treated with warfarin. The trough levels of edoxaban concentration and anti-FXa activity were also compared and correlated with the efficacy and safety of edoxaban vs. warfarin. Compared to non-Asian patients, the Asian population was on average 2 years younger and 20 kg lighter. In the warfarin group, the adjusted risk of ischaemic stroke did not differ significantly for patients of Asian and non-Asian race adjusted hazard ratio (aHR) = 1.12, P = 0.56). Asians treated with warfarin had a higher-adjusted risk of intracranial haemorrhage (ICH: aHR 1.71, P = 0.03) compared with non-Asians. The trough edoxaban concentration and anti-FXa activity were 20–25% lower for Asians compared with non-Asians. Compared to warfarin, higher dose edoxaban significantly reduced ICH while preserving the efficacy of stroke prevention in both Asians and non-Asians. Two of three net clinical outcomes appeared to be more favourably reduced with edoxaban in Asians compared with non-Asians (Pint = 0.063 for primary, 0.037 for secondary, and 0.032 for third net clinical outcomes, respectively). Conclusion Compared to warfarin, higher dose edoxaban preserved the efficacy for stroke prevention and was associated with a favourable safety profile for Asians, which may be due to the lower trough edoxaban concentration and anti-FXa activity achieved in patients of Asian race.