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Background The best periprocedural anticoagulation strategy at the time of pulmonary vein isolation (PVI) is not known. Most centers stop administering warfarin (Coumadin) and use bridging with heparin or enoxaparin. Objective The purpose of this study was to evaluate the efficacy and safety of PVI under therapeutic international normalized ratio (INR). Methods Between January 2005 and December 2008, PVI was performed in 3,052 patients with therapeutic INR (≥1.8) at the time of ablation. All patients were evaluated for ischemic strokes and bleeding complications. Results Mean INR was 2.53 ± 0.62. Only 3 (0.098%) patients had ischemic strokes. One patient had a hemorrhagic stroke on the third day postablation but recovered completely by 1-week follow-up. Bleeding complications occurred in 34 (1.11%) patients; most were minor (0.79%). Major hemorrhagic complications occurred in 10 (0.33%) patients (tamponade in 5, hematomas requiring intervention in 2, transfusion necessary in 3). Conclusion In a large patient population, continuation of Coumadin at a therapeutic INR at the time of PVI without use of heparin or enoxaparin for bridging is a safe and efficacious periprocedural anticoagulation strategy. It is an acceptable and potentially better alternative to strategies that use bridging with heparin or enoxaparin.