Extracorporeal cardiopulmonary resuscitation (ECPR) is commonly initiated for adults experiencing cardiac arrest within the cardiac catheterization lab or the intensive care unit. However, the potential benefit of ECPR for these patients in the emergency department (ED) remains undocumented. This study aims to assess the benefit of ECPR initiated in the ED for patients with out-of-hospital cardiac arrest (OHCA). We conducted a systematic review and meta-analysis of studies comparing ECPR initiated in the ED versus conventional CPR. Relevant articles were identified by searching several databases including PubMed, EMBASE, Web of Science, and Cochrane collaborations up to July 31, 2022. Pooled estimates were calculated using the inverse variance heterogeneity method, while heterogeneity was evaluated using Q and I2 statistics. The risk of bias in included studies was evaluated using validated bias assessment tools. The primary outcome was a favorable neurological outcome at hospital discharge, and the secondary outcome was survival to hospital discharge or 30-day survival. Sensitivity analyses were performed to explore the benefits of ED-initiated ECPR in studies utilizing propensity score (PPS) analysis. Publication bias was assessed using Doi plots and the Luis Furuya-Kanamori (LFK) index. The meta-analysis included a total of eight studies comprising 51,173 patients. ED-initiated ECPR may not be associated with a significant increase in favorable neurological outcomes (odds ratio OR 1.43, 95% confidence interval CI 0.30-6.70, I2 = 96%). However, this intervention may be linked to improved survival to hospital discharge (OR 3.34, 95% CI 2.23-5.01, I2 = 17%). Notably, when analyzing only PPS data, ED-initiated ECPR demonstrated efficacy for both favorable neurological outcomes (OR 1.89, 95% CI 1.26-2.83, I2 = 21%) and survival to hospital discharge (OR 3.37, 95% CI 1.52-7.49, I2 = 57%). Publication bias was detected for primary (LFK index 2.50) and secondary (LFK index 2.14) outcomes. The results of this study indicate that ED-initiated ECPR may not offer significant benefits in terms of favorable neurological outcomes for OHCA patients. However, it may be associated with increased survival to hospital discharge. Future studies should prioritize randomized trials with larger sample sizes and strive for homogeneity in patient populations to obtain more robust evidence in this area.