AIM: To investigate the clinical effects of tirofiban and butylphthalide combined with stent thrombectomy in the treatment of patients with acute cerebral infarction in the ultra-time window. METHODS: A total of 100 patients with ACI beyond time window admitted to our hospital from January 2021 to January 2023 were randomly grouped into the control group (50 cases, treated with stent thrombectomy) and the study group (50 cases, treated with tirofiban and butylphthalide combined with stent thrombectomy), clinical data of patients were collected, and the clinical efficacy, blood lipid levels, coagulation function, neurological function, quality of life, and incidence of adverse reactions were compared between the two groups. RESULTS: Compared with the control group, the total effective rate of the study group obviously increased (P<0.05). Before treatment, there was no obvious difference between the two groups in triacylglycerol (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer (D-D), fibrinogen (FIB), NIHSS score and Barthel index scale (BI) score of patients with ACI beyond time window (P>0.05). After treatment, the TG, TC, LDL-C, FIB, D-D, and NIHSS score of ACI patients in both groups decreased (P<0.05), while HDL-C, PT, APTT, and BI score increased (P<0.05), and the above indicators improved more obviously in the study group (P<0.05). There was no obvious difference in the total incidence of adverse reactions between the two groups (P>0.05). CONCLUSION: The combination of tirofiban and butylphthalide with stent thrombectomy in the treating ACI beyond time window has a definite effect, which can improve the blood lipid level, coagulation function and neurological function of patients, and help to improve the quality of life of patients, with good safety.