BACKGROUND Warfarin reduces the risk of stroke in patients with atrial fibrillation but increas- es the risk of haemorrhage and is difficult to use. Dabigatran is a new oral direct thrombin inhibitor. In this no inferiority trial, we randomly assigned 18.113 patients who had atrial fibrillation and risk of stroke to receive, in a blinded fashion, fixed doses of dabigatran ―110 mg or 150 mg twice daily ― or, in an unblinded fashion, adjusted-dose warfarin. The median duration of the follow-up period was 2.0 years. The primary outcome was stroke or systemic embolism. RESULTS Rates of the primary outcome were 1.69% per year in the warfarin group, as compared with 1.53% per year in the group that received 110 mg of dabigatran (relative risk with dabigatran, 0.91; 95% confidence interval (CI), 0.74 to 1.11; P < 0.001 for noninferity) and 1.11% per year in the group that received 150 mg of dabigatran (relative risk, 0.66; 95% CI, 0.53 to 0.82; P< 0.001 for superiority). The rate of major bleeding was 3.36& per year in the warfarin group, as compared with 2.71% per year in the 110 mg dabigatran group (P= 0.003) and 3.11% per year in the 150 mg dabigatran group (P=0.31). The rate of hemorrhagic stroke was 0.38% per year in the warfarin group as compared with 0.12% per year with 110 mg of dabigatran (P<0.001) and 0.10% per year with 150m mg of dabigatran (P<0.001). The mortality rate was 4.13% per year in the warfarin group, as compared with 3.75% per year with 110 mg of dabigatran (P=0.13) and 3.64% per year with 150 mg of dabigatran (P=0.051). In patients with atrial fibrillation, dabigatran given at a dose of 1110 mg was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin, as well as lower rates of major haemorrhage. Dabigatran administered at a dose of 150 mg, as compared with warfarin, was associated with lower rates of stroke and systemic embolism but similar rates of haemorrhage.