Objective To analyze the clinical characteristics of acute ischemic stroke （AIS） in nonvalvular atrial fibrillation （NVAF） patients with prior anticoagulant therapy. Methods Data of NVAF patients with AIS hospitalized in the Department of Neurology， Xuanwu Hospital of Capital Medical University from January 2016 to December 2021 in the observational study （NCT04080830） was retrospectively analyzed. Patients were divided into the non-anticoagulant， adequate anticoagulant and insufficient anticoagulant groups according to anticoagulant status before onset. The clinical characteristics were compared among the three groups. Results A total of 749 AIS patients with NVAF were recruited， including 661 in non-anticoagulant group， 33 in adequate anticoagulant group and 55 in insufficient anticoagulant group. The rates of massive infarction and the scores of National Institute of Health Stroke Scale （NIHSS） at admission and discharge of the adequate anticoagulant group were lower than those of the non-anticoagulant group［15.2%（5/33）vs 34.2% （226/666），4.00（1.00，7.50）vs 8.00（3.00，15.00），2.00（0，5.00）vs 4.00（1.00，12.00）］. The proportion of patients with scores of Modified Rankin Scale （mRS） ≤ 2 at discharge in the adequate anticoagulant group were higher than that in the non-anticoagulant group ［66.7%（22/33）vs 44.0%（226/666）］. The differences were statistically significant （all P ＜ 0.05）. The proportion of intravenous thrombolysis in the adequate anticoagulant group and the insufficient anticoagulant group was lower than that in the non-anticoagulant group［3.0%（1/33） and 3.6% （2/55）vs 5.6% （37/666）］， and the difference was statistically significant （P ＜ 0.01）. Compared with the nonanticoagulant group and the insufficient anticoagulant group， patients in the adequate anticoagulant group had higher rates of cardioembolic/ large-artery AIS ［42.4%（14/33）vs 21.8%（144/666） and 16.4%（9/55）， P＜ 0.01］. Conclusions Adequate anticoagulant therapy in NVAF patients might be associated with milder ischemic stroke severity and better outcomes at discharge. The mechanism of competitive large artery atherosclerosis induced AIS may be one of the reasons why adequate anticoagulant treatment fails to effectively prevent and control AIS risk in NVAF patients.