Atrial fibrillation (AF) is a common arrhythmia that is associated with an increased risk for vascular events, particularly stroke. Two different therapies have been extensively evaluated for prevention of vascular events in AF: oral anticoagulation (such as warfarin), and aspirin. Placebo-controlled trials of warfarin have been performed and summarized in a meta-analysis. There is clear evidence of a benefit, with a relative risk reduction in stroke of 67% and in total vascular events of 42%. Aspirin also has been studied and is effective, but with a more modest benefit (relative risk reduction of 22%). Several studies have compared warfarin and aspirin, and showed a clear benefit in favor of warfarin for reduction of vascular events and stroke. Compared to aspirin, the risk of major hemorrhage with oral anticoagulation is increased by 70% to 100%. Current practice guidelines recommend oral anticoagulation therapy for high-risk patients with AF, unless there is an increased risk for bleeding. Nonetheless, oral anticoagulation therapy with drugs such as warfarin is difficult for both patients and physicians because of the increased risk for bleeding and the need for ongoing monitoring of coagulation status. Many patients do not receive anticoagulation therapy despite its proven benefits.