Background: A number of studies have demonstrated the efficacy of oral anticoagulant therapy in reducing the risk of stroke and systemic embolism in patients with nonrheumatic atrial fibrillation. However, both the targeted and the actual levels of anticoagulation differed widely among the studies, and a number of studies failed to report standardized prothrombin-time ratios as international normalized ratios (INRs). We therefore performed an analysis to determine the intensity of oral anticoagulant therapy in nonrheumatic atrial fibrillation that provides the best balance between the prevention of thromboembolism and the occurrence of bleeding complications. Methods: We calculated INR-specific incidence rates for both ischemic and major hemorrhagic events occurring in 214 patients who received anticoagulant therapy in the European Atrial Fibrillation Trial, a secondary-prevention trial in patients with nonrheumatic atrial fibrillation and a recent episode of minor cerebral ischemia. Results: The optimal intensity of anticoagulation was found to lie between an INR of 2.0 and an INR of 3.9. No treatment effect was apparent with anticoagulation below an INR of 2.0. The rate of thromboembolic events was lowest at INRs from 2.0 to 3.9, and most major bleeding complications occurred with treatment at intensities with INRs of 5.0 or above. Conclusions: To achieve optimal levels of anticoagulation with the lowest risk in patients with atrial fibrillation and a recent episode of cerebral ischemia, the target value for the INR should be set at 3.0, and values below 2.0 and above 5.0 should be avoided.