Objective: To explore the clinical effect of Alteplase (rt-PA) combined with stent thrombectomy in the treatment of Acute cerebral infarction (ACI). Methods: The clinical data of 60 patients with ACI admitted to our hospital from February 2022 to February 2024 were retrospectively collected. The patients were divided into the control group (30 cases, treated with rt-PA intravenous thrombolysis) and the observation group (30 cases, treated with rt-PA intravenous thrombolysis combined with stent thrombectomy) according to different treatment methods. The neurological function (NIHSS score), cerebral hemodynamics [Mean Blood Flow Velocity (Vm), Pulsatility Index (PI), Resistive Index (RI)], prognosis and incidence of adverse events of the two groups were collected and compared. Results: At 7 days and 14 days of treatment, the NHISS scores of both groups were significantly lower than those before treatment, and the NIHSS scores of the observation group at 7 days and 14 days after treatment were significantly lower than those of the control group (P < 0.05). After 14 days of treatment, the Vm of both groups was significantly increased compared with that before treatment, while the PI and RI were significantly decreased. Moreover, the Vm of the observation group after 14 days of treatment was significantly higher than that of the control group, and the PI and RI were significantly lower than those of the control group (P < 0.05). The overall excellent and good prognosis rate of the observation group at 90 days of follow-up was significantly higher than that of the control group (P < 0.05). There was no significant difference in the total incidence of adverse events between the two groups (P > 0.05). Conclusion: rt-PA intravenous thrombolysis combined with stent thrombectomy in the treatment of ACI patients can improve the neurological function of patients, optimize cerebral blood flow perfusion and prognosis, and has good safety.