BACKGROUND: Contemporary radiofrequency catheter ablation (RFCA) approaches for atrial fibrillation (AF) have reached an efficacy "ceiling". Ethanol infusion into the vein of Marshall (EI-VOM) has shown potential in preliminary studies. Data on EI-VOM are largely limited to small single-center reports, and clinical benefits and risks have not been systematically examined. Therefore, we performed a meta-analysis to assess the feasibility, efficacy, and safety of EI-VOM for AF. METHODS: All studies evaluating EI-VOM for AF were initially searched from four electronic search engines: PubMed, Web of Science, Cochrane Library, and SinoMed. We used RevMan5.4 to calculate pooled outcomes of randomized controlled trial and cohort studies. We also performed single-arm meta-analyses using Open Meta-Analyst. RESULTS: We included a total of 10 studies with 1322 patients. Successful EI-VOM was performed in 86.7% (95% CI 81.9-91.4%) of patients. For persistent AF patients, the recurrence of AF and/or atrial tachycardia (AT) was significantly lower in the EI-VOM combined with RFCA group compared with RFCA alone group (RR 0.58, 95% CI 0.35 to 0.96, p = 0.04). EI-VOM combined with RFCA significantly increased the rate of bidirectional mitral isthmus block compared with RFCA alone in AF patients (RR 1.50, 95% CI 1.34 to 1.67, p < 0.001). There were nine cardiac tamponades observed in 644 patients (PR 0.8%, 95% CI 0.1-1.5%) who were performed EI-VOM combined with RFCA. CONCLUSIONS: Our meta-analysis brings encouraging evidence that adjuvant EI-VOM reduces AF and/or AT recurrence rate in persistent AF patients and increases the success rate of bidirectional mitral isthmus block.