Background: The occurrence of early neurological deterioration (END) following intravenous thrombolysis (IVT) is considered a particularly ominous clinical event and is strongly correlated with poor outcomes. Initiating tirofiban within 24 h after IVT has been suggested as a better treatment option to achieve long-term functional outcomes. However, the rationality of this remedy is a controversial. The purpose of the study was to evaluate the safety and efficacy of early intravenous tirofiban administration after IVT in patients with acute ischemic stroke (AIS). Methods: Databases including PubMed, EMBASE, Cochrane Library, and Web of Science were searched for clinical trials on early tirofiban implementation after IVT in patients with AIS from inception to September 2022. Odds ratios (ORs) were generated for dichotomous variants via meta-analysis using STATA 17.0 MP. Results: Five clinical trials with 725 patients were eligible. The study outcomes demonstrated that early tirofiban administration after IVT was not associated with symptomatic intracranial hemorrhage (Odds ratios [OR], 0.78; 95%confidence interval [CI], 0.22 - 2.74; P=0.70), asymptomatic intracranial hemorrhage (OR, 1.11; 95%CI, 0.52 - 2.37; P=0.80), systemic bleeding (OR, 0.97; 95%CI, 0.42 - 2.23; P=0.94), and death (OR, 1.05; 95%CI, 0.47 - 2.31; P=0.91), but may reduce the incidence of END (OR, 0.09; 95% CI, 0.02 - 0.50; P=0.01), and was significantly associated with 90-day excellent (modified Rankin scale[mRS] score 0–1) (OR, 2.01; 95% CI, 1.35 - 3.02; P=0.00) and favorable (mRS score 0–2) (OR, 2.30; 95% CI, 1.63 - 3.23; P=0.00) functional outcomes. Conclusion: The early intravenous administration of tirofiban after IVT in patients with AIS may be a safe and effective treatment strategy that improves long-term neurological functional outcomes without increasing the risk of adverse events.