Objective To explore the application of 640-slice CT perfusion imaging (CTP) in the reperfusion therapy of acute ischemic stroke. Methods 52 cases of patients with acute ischemic stroke who were admitted to our emergency department from January 2016 to January 2018 were selected within 4.5 hours of onset, and were given intravenous recombinant tissue plasminogen activator (rt-PA) thrombolytic therapy, and they were given CT plain scan and CTP before treatment. According to whether or not hemorrhagic transformation (HT) occurred after treatment, the patients were divided into HT occurrence group and HT non-occurrence group. The CTP-related parameters [cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), permeability surface (PS)] were compared between the lesion side and the healthy side, HT occurrence group, and HT non-occurrence group. And the correlation between CTP-related parameter and HT occurrence was analyzed. Results All the 52 patients had good CT plain scans and CTP images, and CT plain scans of 36 patients showed low-density ischemic lesions and local disappeared sulcus. All patients had large-scale abnormal hypoperfusion areas corresponding to clinical symptoms in CTP images. The values of CBF, CBV and MTT in the lesion side were lower than those in the healthy side (P<0.05) while the PS value was higher than that in the healthy side (P<0.05). The values of CBF and CBV in the lesion side of HT occurrence group were lower than those of HT non-occurrence group (P<0.05) while the PS value was higher than that in HT non-occurrence group (P<0.05). There was significant correlation between CBV, CBF and PS and HT (P<0.05), and CBV and CBF were negatively correlated with HT, and PS was positively correlated with HT. Conclusion 640-slice CTP has a good predictive value for HT in patients with acute ischemic stroke and reperfusion.