Objective To investigate the influence of tirofiban during mechanical thrombectomy (MT) on platelet count, NIHSS score and prognosis in patients with acute cerebral infarction (ACI). Methods ACI patients who received MT in the hospital from March 2021 to March 2024 were included. According to whether tirofiban was given during surgery, the patients were divided into tirofiban group and MT group. The MT group was given Trevo stent for MT treatment, while the tirofiban group was treated with intra-arterial infusion of tirofiban during surgery on the basis of the MT group. After excluding the influence of confounding factors of baseline data by propensity matching score method (caliper=0.02), 66 patients with comparable baseline data were obtained in each group. The short-term efficacy, National Institutes of Health Stroke Scale (NIHSS) score before surgery and at 1 day and 7 days after surgery, postoperative blood flow grading, hematological indicators ［platelet count (PLT), platelet aggregation rate, platelet adhesion rate, whole blood viscosity, plasma viscosity］ before surgery and at 1 and 7 days after surgery and prognosis status ［modified Rankin scale (mRS)］ within 90 days of follow-up were compared between groups, and the safety evaluation was performed. Results The total effective rate in tirofiban group (96.97%) was significantly higher than that in MT group (87.88%) (P＜0.05). The NIHSS score in both groups was decreased at 1 day after surgery (P＞0.05), and was significantly declined at 7 days after surgery (P＜0.05), and the NIHSS score in tirofiban group was significantly lower than that in MT group (P＜0.05). There was no significant difference in postoperative blood flow grading between groups (P＞0.05), but the number of patients with postoperative blood flow grade 3 was significantly more in tirofiban group than that in MT group (P＜0.05). At 1 day and 7 days after surgery, the PLT, platelet aggregation rate, platelet adhesion rate, whole blood viscosity and plasma viscosity in both groups were decreased significantly with time (P＜0.05), and the above indicators in tirofiban group at 1 day and 7 days after surgery were significantly lower than those in MT group (P＜0.05). Within 90 days of follow-up, there were no significant differences in the incidence rates of vascular reocclusion, intracranial hemorrhage and death within 90 days between the two groups (P＞0.05), but the rate of good prognosis in tirofiban group was significantly higher than that in MT group (P＜0.05). During 90 days of follow-up, no stent displacement or adverse drug reactions were observed in both groups. Conclusion The application of tirofiban during MT can enhance the short-term efficacy of ACI patients, improve the neurological function, postoperative blood flow grading, platelet agglutination and hemorheology, and improve the prognosis outcome, and it has good safety