Acute ischemic stroke is a cerebrovascular disease associated with high disability and mortality. Tirofiban, a platelet glycoprotein IIb/IIIa receptor antagonist, is used in conjunction with IV thrombolysis for bridging therapy, but its effectiveness and safety compared with IV thrombolysis alone in patients with stroke are not well-established.The aim was to conduct a systematic review and meta-analysis to determine whether tirofiban increased the risk of poor outcomes and mortality in patients with stroke and accepted IV thrombolysis within the time window, or whether it can improve functional prognosis in follow-up.PubMed, EMBASE, Cochrane Library, and Web of Science were searched for randomized controlled trials and observational studies from inception to June 15, 2023. Trials reporting the effectiveness and safety of tirofiban bridging after IV thrombolysis compared with thrombolysis only in patients with acute ischemic stroke were included.Two randomized controlled trials and 5 observational studies with 771 participants were included. Tirofiban plus IV thrombolysis significantly favored improved neurologic function based on both modified Rankin Scale 0-2 (risk ratio [RR] 1.38; p < 0.001) and 0-1 (RR 1.54; p < 0.001) at month 3. There was no significant difference in 3-month mortality risk, symptomatic intracranial hemorrhage on the seventh day, and systemic bleeding between the 2 groups (RR 1.11; p = 0.780; RR 0.68; p = 0.670; RR 1.97; p = 0.510).Tirofiban plus intravenous thrombolysis was associated with better functional outcomes, but not symptomatic intracranial hemorrhage, systemic bleedings, or mortality among patients with acute ischemic stroke compared with IV thrombolysis only. Further studies should focus on its safety profile and application to target patients.Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.