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Timely reperfusion is key to ensuring better outcomes in patients with large-vessel acute ischemic stroke. The role of thrombolysis (IVT) prior to endovascular thrombectomy (EVT) remains controversial, with previous studies yielding contradictory findings. This meta-analysis compares the efficacy and safety of IVT prior to EVT in acute ischemic stroke. A comprehensive literature search was performed across PubMed MEDLINE, Cochrane Library, ScienceDirect, Google Scholar, and ClinicalTrials.gov for eligible studies. Twenty-one studies (8 RCTs, 13 observational studies; n = 10,538) published between 2013 and 2025 were included in the meta-analysis. The primary outcome was 90-day functional independence (mRS 0-2), with secondary outcomes including successful reperfusion (mTICI = 2b), 90-day mortality, symptomatic intracranial hemorrhage (sICH), and any ICH. Pooled risk ratios (RR) were calculated. The certainty of evidence was evaluated using the GRADE framework. Bridging therapy resulted in higher rates of 90-day functional independence (RR 1.12, 95% confidence intervals [CI] 1.05-1.20), successful reperfusion (RR 1.04, 95% CI 1.01-1.06), and lower 90-day mortality (RR 0.80, 95% CI 0.69-0.91). However, the benefit was offset by significantly increased risk of sICH (RR 1.35, 95% CI 1.03-1.65). Results were consistent for subgroups with similar baseline NIHSS scores, time to groin puncture, full-dose alteplase, and cohorts, while RCTs and low-dose alteplase did not show significant results. While observational data suggest a clinical advantage, randomized evidence does not consistently demonstrate superiority of bridging therapy over EVT alone. In conclusion, these findings support individualized treatment decisions based on workflow efficiency, stroke severity, and bleeding risk rather than a universal approach.

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