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Recent studies have reported that endovascular thrombectomy (ET) may improve neurological outcomes in large-core stroke.We performed a systematic review and meta-analysis to compare the pooled efficacy and safety of ET and of the best medical treatment among patients with large-core stroke.We searched the PubMed/MEDLINE, Scopus, and Cochrane databases from inception to November 2023. The inclusion criteria were randomized controlled trials (RCTs) comparing ET and the best medical treatment available among patients with large-core stroke (Alberta Stroke Program Early Computed Tomography Score [ASPECTS] < 6 or ischemic core > 50 mL on perfusion imaging) within 24 hours of symptom onset.We included 6 RTCs comprising 1,887 patients (ET group: n = 945). Endovascular thrombectomy was associated with good neurological outcomes (odds ratio [OR]: 2.92; 95% confidence interval [95%CI]: 2.17-3.93), or independent walking (OR: 2.22; 95%CI: 1.72-2.86). Trial sequential analysis confirmed a robust statistical significance for good neurological outcomes favoring ET. Endovascular thrombectomy was associated with higher risks of developing intracranial bleeding (OR: 2.65; 95%CI: 1.35-5.22) and symptomatic intracranial bleeding (OR: 1.83; 95%CI: 1.14-2.94). There were no differences between the groups regarding mortality or decompressive craniectomy. Patients submitted to non-contrast computed tomography (CT) with CT angiography (CTA) scans were analyzed separately and showed good neurological outcomes, comparable to those of the patients submitted to other imaging modalities (OR: 3.24; 95%CI: 1.52-6.92).Endovascular thrombectomy was associated with good neurological outcomes and independent walking in patients with large-core acute ischemic stroke. However, it was also associated with an increased risk of developing intracranial bleeding. Non-contrast head CT with CTA scans may be appropriate for screening patients to undergo ET.