Warfarin is underused because it has many disadvantages for clinical use despite it has been used more than a half century as an only oral anticoagulant. Dabigatran is a direct thrombin inhibitor, which is not metabolized by cytochrome P450, and thus does not require blood coagulation monitoring or vitamin K intake limitation, or produce drug interaction. RE-LY was a randomized controlled trial to prove non-inferiority of dabigatran to warfarin in 18,113 high risk patients with non-valvular atrial fibrillation. The results showed that stroke or systemic embolism was less frequent in patients on 150 mg dabigatran, major hemorrhage was less frequent in patients on 110 mg dabigatran, and hemorrhagic stroke was less frequent in patients on both 110 mg and 150 mg dabigatran than in patients on warfarin. Dabigatran is expected to be approved as a more effective and safer oral anticoagulant than warfarin for stroke prevention in patients with atrial fibrillation. Randomized controlled trials of many factor Xa inhibitors in comparison with warfarin are also ongoing in patients with atrial fibrillation.