Atrial fibrillation (AF) is an independent risk factor for ischemic stroke and warfarin related anticoagulation has been recommended as an effective treatment for stroke prevention. We aimed to determine whether pre-stroke oral anticoagulation therapy would reduce initial stroke severity in AF patients with first-ever ischemic stroke. We identified consecutive patients who developed first-ever ischemic stroke and were eligible for anticoagulation therapy from the China National Stroke Registry. Multivariate logistic analysis was used to assess the association between warfarin usage and initial stroke severity, measured by the National Institutes of Health Stroke Scale (NIHSS) and the Glasgow Coma Scale (GCS). Of 9519 patients, 1140 (11.98%) had AF, including 440 (38.6%) without known AF before presentation, 561 (49.2%) with known AF but not taking warfarin, and 139 (12.2%) with known AF who were taking warfarin. Compared to patients with known AF but not on warfarin, the odds ratio (OR) of having a major stroke (NIHSS >= 4) was lower in patients with known AF who were on warfarin (OR = 0.68; 95% confidence interval [CI] 0.57-0.84). The OR of developing a severe coma (GCS 3-8) was also reduced in the warfarin group (OR = 0.71; 95% CI 0.56-0.91). In conclusion, pre-stroke warfarin therapy lowered the severity of the first-ever ischemic stroke in patients with known AF. Considering its efficacy in stroke prevention and the significant under-usage of warfarin in China, the primary prevention of stroke in AF patients should be reinforced. (C) 2014 Published by Elsevier Ltd.