Background: Oral anticoagulation therapy reduces risk of vascular events in patients with atrial fibrillation. However, long- term monitoring is necessary and many patients cannot achieve optimum anticoagulation. We assessed whether clopidogrel plus aspirin was non- inferior to oral anticoagulation therapy for prevention of vascular events. Methods: Patients were enrolled if they had atrial fibrillation plus one or more risk factor for stroke, and were randomly allocated to receive oral anticoagulation therapy (target international normalised ratio of 2.0- 3.0; n=3371)- or clopidogrel (75 mg per day) plus aspirin (75- 100 mg per day recommended; n=3335). Outcome events were adjudicated by a blinded committee. Primary outcome was first occurrence of stroke, non- CNS systemic embolus, myocardial infarction, or vascular death. Analyses were by intention- to- treat. This study is registered with ClinicalTrials.gov, number NCT00243178. Results: The study was stopped early because of clear evidence of superiority of oral anticoagulation therapy. There were 165 primary events in patients on oral anticoagulation therapy (annual risk 3.93% ) and 234 in those on clopidogrel plus aspirin (annual risk 5.60% ; relative risk 1.44 (1.18- 1.76); p=0.0003). Patients on oral anticoagulation therapy who were already receiving this treatment at study entry had a trend towards a greater reduction in vascular events (relative risk 1.50, 95% CI 1.19- 1.89) and a significantly (p=0.03 for interaction) lower risk of major bleeding with oral anticoagulation therapy (1.30; 0.94- 1.79) than patients not on this treatment at study entry (1.27, 0.85- 1.89 and 0.59, 0.32- 1.08, respectively). Conclusion: Oral anticoagulation therapy is superior to clopidogrel plus aspirin for prevention of vascular events in patients with atrial fibrillation at high risk of stroke, especially in those already taking oral anticoagulation therapy. Background: Oral anticoagulation therapy reduces risk of vascular events in patients with atrial fibrillation. However, long- term monitoring is necessary and many patients can not achieve optimum anticoagulation. We suppl ine clopidogrel plus aspirin was non- inferior to oral anticoagulation therapy for prevention of vascular events. Methods: Patients were enrolled if they had atrial fibrillation plus one or more risk factor for stroke, and were randomly allocated to receive oral anticoagulation therapy (target international normalized ratio of 2.0-3.0; n = 3371) -or clopidogrel (75 mg per day plus aspirin (75-100 mg per day recommended; n = 3335). Outcome events were adjudicated by a blinded committee. Primary outcome was first occurrence of stroke, non- CNS systemic embolus, myocardial infarction, or vascular death. were by intention-to- treat. This study was registered with ClinicalTrials.gov, number NCT00243178. Results: The study was stopped early because of clear e There were 165 primary events in patients on oral anticoagulation therapy (annual risk 3.93%) and 234 in those on clopidogrel plus aspirin (annual risk 5.60%; relative risk 1.44 (1.18-1.76); p = 0.0003). Patients on oral anticoagulation therapy who were already receiving this treatment at study entry had a trend towards a greater reduction in vascular events (relative risk 1.50, 95% CI 1.19-1.89) and a significantly (p = 0.03 for interaction) lower risk of major bleeding with oral anticoagulation therapy (1.30; 0.94-1.79) than patients not on this treatment at study entry (1.27, 0.85-1.89 and 0.59, 0.32-1.08, respectively). Conclusion: Oral anticoagulation therapy is superior to clopidogrel plus aspirin for prevention of vascular events in patients with atrial fibrillation at high risk of stroke, especially in those already taking oral anticoagulation therapy.