Introduction: With one person in Canada suffering an out-of-hospital cardiac arrest (OHCA) every 12 minutes and an estimated survival to hospital discharge with good neurologic function ranging from 3 to 16%, OHCA represents a major source of morbidity and mortality. An evolving adjunct for resuscitation of OHCA patients is the use of extracorporeal membrane oxygenation-assisted CPR (ECPR). The purpose of this systematic review is to investigate the survival to hospital discharge with good neurologic recovery in patients suffering from OHCA treated with ECPR compared to those who received standard advanced cardiac life support with conventional CPR (CCPR) alone. Methods: A systematic database search of both MEDLINE & EMBASE was performed up until September 2016 to identify studies with ≥5 patients reporting ECPR use in adults (age ≥16 years) with OHCA. Only studies reporting survival to hospital discharge were included. All identified studies were assessed independently using pre-determined inclusion criteria by two reviewers. Study quality and risk of bias were evaluated using the Newcastle Ottawa regulations assessment scale. Results: Of the 1065 records identified, 54 studies met all inclusion criteria. Inter-rater reliability was high with a kappa statistic of 0.85. The majority of studies were comprised of case series (n=45) of ECPR with 5 to 83 patients/study. Out of the 45 case series, 37 presented neurologic data at hospital discharge and demonstrated a broad range of patients surviving with good neurologic outcome (0 to 71.4%). Only 9 cohort studies with relevant control group (CCPR) were identified (38 to 21750 patients/study). Preliminary analysis demonstrated that 6 cohort studies were sufficient quality to compare ECPR to CCPR. All 6 studies showed significantly increased survival to hospital discharge with good neurologic recovery (ECPR 10.6 to 41.6% vs CCPR 1.5 to 7.7%, respectively). Conclusion: Given the paucity of studies using appropriate comparators to evaluate the impact of ECMO, our confidence in a clinically relevant difference in outcomes compared to current standards of care for OHCA remains weak. Interestingly, a limited number of studies with suitable controls demonstrated a potential benefit associated with ECPR in the management of OHCA in selected patients. In this state of equipoise, high quality RCT data is urgently needed.