Objective It is controversial whether urokinase thrombolysis should be administered in acute ischemic stroke patients with atrial fibrillation(AF).This study aimed to explore the efficacy of urokinase thrombolysis in these patients.Methods This is a retrospective case-control study.Consecutive patients with acute ischemic stroke who received intravenous urokinase within 6 hours of symptom onset were included between April 2006 and January 2012.These patients who met the inclusion criteria were classified into two groups: AF(n=26) and non-AF(n=60) groups.National Institutes of Health Stroke Scale(NIHSS) and modified Rankin Scale were used to evaluate therapeutic effects.Results There was no significant difference in the efficacy between the two groups(57.7% vs.56.7%,P0.05).Ninety days after urokinase treatment,functional recovery was seen in 57.7% of patients in the AF group compared with 65.0% in the non-AF group(P0.05).The AF group demonstrated higher incidences of intracranial hemorrhage,symptomatic intracranial hemorrhage and mortality rate than the non-AF group,but the differences were not significant(P0.05).Conclusions The patients with acute ischemic stroke,no matter whether they have AF or not,can benefit from urokinase thrombolysis.AF does not seem to affect the efficacy of urokinase thrombolysis in patients with acute ischemic stroke.Thrombolysis therapy is recommended for acute ischemic stroke with AF.