There is limited evidence comparing the use of extracorporeal cardiopulmonary resuscitation (ECPR) to CPR in the management of refractory out-of-hospital cardiac arrest (OHCA). We conducted a systematic review and meta-analysis to compare survival and neurologic outcomes associated with ECPR versus CPR in the management of OHCA. We searched PubMed, EMBASE, and Scopus to identify observational studies and randomized controlled trials comparing ECPR and CPR. We used the Newcastle–Ottawa Scale and Cochrane’s risk-of-bias tool to assess studies’ quality. We used random-effects models to compare outcomes between the pooled populations and moderator analysis to identify sources of heterogeneity and perform subgroup analysis. We identified 2088 articles and included 13, with 18,620 patients with OHCA. A total of 16,701 received CPR and 1919 received ECPR. Compared with CPR, ECPR was associated with higher odds of achieving favorable neurologic outcomes at 3 (OR 5, 95% CI 1.90–13.1, p < 0.01) and 6 months (OR 4.44, 95% CI 2.3–8.5, p < 0.01). We did not find a significant survival benefit or impact on neurologic outcomes at hospital discharge or 1 month following arrest. ECPR is a promising but resource-intensive intervention with the potential to improve long-term outcomes among patients with OHCA.