Objective To investigate the relationship between cerebral blood perfusion (CTP) parameters and prognosis of patients with acute cerebral infarction (ACI) after thrombolytic therapy. Methods A retrospective clinical analysis was performed on 139 patients with ACI who received intravenous thrombolysis in our hospital from September 2021 to September 2024. According to the prognosis of patients 3 months after treatment, they were divided into a good prognosis group (96 cases) and a poor prognosis group (43 cases). CTP examination results within 24 hours after thrombolysis were compared between the two groups. Receiver operating characteristic curve (ROC) was used to predict the outcome of the patients, and the influencing factors of the outcome were analyzed by Logistic regression model. Results There were no significant differences in BMI, thrombolysis time window, gender, smoking, drinking and co-morbidity between the good prognosis group and the poor prognosis group (P>0.05). The age of patients in the poor prognosis group was higher than that in the good prognosis group (P<0.05). The measured values of CBV and CBF in the poor prognosis group after thrombolytic therapy were lower than those in the good prognosis group (P<0.05). The MTT and TTP values of patients with poor prognosis after thrombolytic therapy were higher than those of patients with good prognosis (P<0.05). The area under ROC curve AUC values of CBV, CBF, MTT, TTP and other indicators combined to predict the adverse prognosis of ACI patients after intravenous thrombolytic therapy were 0.692, 0.667, 0.615, 0.654 and 0.891, respectively. Multivariate model analysis showed that the lower the CBV and CBF of ACI patients after intravenous thrombolysis, the older the patient, the higher the NIHSS score at admission, and the higher the plasma D-D value were independent risk factors for poor prognosis (P<0.05). Conclusion For ACI patients receiving intravenous thrombolysis treatment, CTP examination can be performed to analyze the recovery of perfusion levels, which can predict the early prognosis and recovery effect of patients. The decrease in CBV and CBF levels is closely related to poor prognosis of patients.