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Introduction The efficacy of endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) resulting from distal medium vessel occlusion (DMVO) remains uncertain.Aim of Study This systematic review and meta-analysis aimed to provide a comprehensive assessment of EVT in AIS due to DMVO, based on evidence derived from randomized controlled trials (RCTs).Method We systematically reviewed four electronic databases to find relevant studies. Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated for categorical and continuous outcomes, respectively. Significant heterogenicity was resolved with leave-one-out influence analysis.Results There were 601 patients in EVT plus best medical treatment (BMT) group and 623 patients in BMT alone group. Findings showed a significantly higher rate of serious adverse events (RR=1.3, 95%CI: 1.1 – 1.5, P< 0.01) and sICH (RR=3.3, 95%CI: 1.8 – 5.9, P< 0.01) in thrombectomy than control group. There was no significant difference between two groups in 90-day mRS 0–1, mRS 0–2, and mortality. Subgroup analysis, including the three DMVO trials and the two secondary analyses of previous LVO RCTs, confirmed the prior findings. Leave-one-out influence analysis showed no significant heterogeneity in any primary and secondary outcomes.Conclusion Our findings indicate that while EVT does not provide a significant advantage over BMT alone in improving functional outcomes for patients with DMVO, it is associated with an increased risk of hemorrhagic complications. These results underscore the importance of a cautious approach when considering EVT for DMVO and emphasize the need for further RCTs to optimize treatment strategies.Conflict of Interest No