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Background Asian population are at increased risk of bleeding during the warfarin treatment,so the recommended optimal international normalized ratio (INR) level may be lower in Asians than in Westerners.The aim of this prospective multicenter study was to determine the optimal INR level in Thai patients with non-valvular atrial fibrillation (NVAF).Methods Patients with NVAF who were on warfarin for stroke prevention were recruited from 27 hospitals in the nationwide COOL-AF registry in Thailand.We collected demographic data,medical history,risk factors for stroke and bleeding,concomitant disease,electrocardiogram and laboratory data including INR and antithrombotic medications.Outcome measurements included ischemic stroke/transient ischemic attack (TIA) and major bleeding.Optimal INR level was assessed by the calculation of incidence density for six INR ranges (＜ 1.5,1.5-1.99,2-2.49,2.5-2.99,3-3.49,and ≥ 3.5).Results A total of 2,232 patients were included.The mean age of patients was 68.5 ± 10.6 years.The mean follow-up duration was 25.7 ± 10.6 months.There were 63 ischemic stroke/TIA and 112 major bleeding events.The lowest prevalence of ischemic stroke/TIA and major bleeding events occurred within the INR range of 2.0-2.99 for patients ＜ 70 years and 1.5-2.99 for patients ≥ 70 years.Conclusions The INR range associated with the lowest risk of ischemic stroke/TIA and bleeding in the Thai population was 2.0-2.99 for patients ＜ 70 years and 1.5-2.99 for patients ≥ 70 years.The rates of major bleeding and ischemic stroke/TIA were both higher than the rates reported in Western population.