There is an increased risk of stroke and other cardiovascular events in patients with atrial fibrillation (AF). Three meta-analyses of randomized clinical trials (RCTs) comparing oral anticoagulants (OAC) with aspirin (ASA) arrived at different conclusions regarding the relative efficacy of these agents to prevent ischemic stroke in AF patients. This article summarizes a recently published individual patient meta-analysis of all published RCTs comparing OAC and ASA in AF. In total, 4052 patients randomized to OAC or ASA were similar regarding important prognostic factors. Patients receiving OAC had a significantly lower risk of any stroke (hazard ratio [HR] 0.54 [95% CI 0.43-0.71]), ischemic stroke (HR 0.48 [0.37-0.63]), or cardiovascular events (HR 0.71 [0.59-0.85]). Patients receiving OAC were more likely to experience major bleeding (HR 1.71 [1.21-2.41]). The benefit of OAC was most prominent in patients at a high risk of stroke and other cardiovascular events, such as patients with hypertension, diabetes, or previous cerebrovascular events. Overall, OAC improves outcomes for cardiovascular events in AF patients but modestly increases the absolute risk of major bleeding. Since high-risk AF patients appear to benefit most from OAC, determining stroke risk in AF patients is very important.