Objective: Intravenous administration of recombinant tissue plasminogen activator (rtPA) is known as the only approved treatment for acute ischemic stroke. However, it is still controversial whether acute ischemic stroke patients with atrial fibrillation should receive rtPA therapy. Methods: We studied 99 patients altogether who belonged to three different groups based on the patient characteristics: (1) atrial fibrillation rtPA-treated group consisting of 22 ischemic stroke patients with atrial fibrillation treated with rtPA within 4.5 hours after the onset of stroke; (2) atrial fibrillation non-rtPA-treated group consisting of 44 acute ischemic stroke patients with atrial fibrillation matching in age and baseline National Institutes of Health Stroke Scale (NIHSS); (3) the non-atrial fibrillation rtPA-treated group consisting of 33 patients without atrial fibrillation treated with rtPA. Results: The median time for the administration of rtPA was 199.6 +/- 50.0 minutes. More patients had favorable outcomes (90 day modified Rankin Scale 0-1) in the atrial fibrillation rtPA-treated group than the atrial fibrillation non-rtPA-treated group (36.4 versus 13.6%; odds ratio=2.667; 95% confidence interval: 1.056-6.735; p=0.033). The mortality at day 90 was lower in the rtPA-treated group than the non-rtPA-treated group (18.2 versus 20.5%; p=0.827), although the incidence of symptomatic intracranial hemorrhage was higher (18.2 versus 6.8%; p=0.184). Patients in the atrial fibrillation rtPA-treated group had fewer favorable outcomes than non-atrial fibrillation rtPA-treated group (36.4 versus 51.6%; p=0.076), but their baseline NIHSS was higher (12.0 +/- 7.1 versus 9.1 +/- 7.3; p=0.161). Conclusion: As compared with non-rtPA-treated patients, rtPA treated within 4.5 hours after the onset of stroke significantly improved clinical outcomes in atrial fibrillation patients. Thrombolytic treatment increases intracranial hemorrhage rate but does not increase mortality.