Atrial fibrillation (AF) is an independent risk factor for intracranial hemorrhage in patients receiving recombinant-tissue-type plasminogen activator (rt-PA) thrombolytic therapy. Research showed that patients with acute ischemic stroke (AIS) could benefit from multimode computed-tomography-(CT-) guided intravenous thrombolysis over 4.5 hours. The medical data of patients with AIS in our center were retrospectively reviewed, and the data of the multimode CT-guided thrombolytic therapy or nonthrombolytic therapy within different time windows (3-9 hours) were evaluated. 134 AIS cases were selected successfully and divided into three groups: patients with AF treated by rt-PA (AF rt-PA), patients with AF not treated by rt-PA (AF non-rt-PA), and patients without AF treated by rt-PA (non-AF rt-PA). After correcting for the baseline NIH Stroke Scale (NIHSS), sex, age, and hypertension data, the comparison results showed that the NIHSS improved significantly at hospital discharge for rt-PA-treated patients (n = 47) compared to non-rt-PA-treated patients with AIS (n = 31) with AF (P = 0.0156). The NIHSS evaluation at 90 days of follow-up also improved in rt-PA-treated patients (P = 0.0157). The NIHSS at hospital discharge was higher in AF rt-PA-treated patients compared to non-AF rt-PAtreated patients (P = 0.0167) after correction; the difference was not statistically significant at 90 days of follow-up (P = 0.091). Our research showed that the neural function improved after 3-9 hours of thrombolytic therapy with rt-PA in patients with AIS and AF. If there is no thrombolytic taboo, the patients could benefit from the thrombolytic therapy, although the onset time window has been extended to 9 hours.