Summary: Extracorporeal membrane oxygenation (ECMO) is used in cardiopulmonary resuscitation (CPR) of refractory cardiac arrest. The authors used a 2 × 2 study design to compare ECMO versus CPR and epinephrine versus placebo in a porcine model of ischemic refractory ventricular fibrillation (VF). Pigs underwent 5 min of untreated VF and 10 min of CPR, and were randomized to receive epinephrine versus placebo for another 35 min. Animals were further randomized to left anterior descending artery (LAD) reperfusion at minute 45 with ongoing CPR versus venoarterial ECMO cannulation at minute 45 of CPR and subsequent LAD reperfusion. Four-hour survival was improved with ECMO whereas epinephrine showed no effect. Key Words: advanced cardiopulmonary life support, cardiac arrest, cardiopulmonary resuscitation, ECMO, extracorporeal membrane oxygenation, ischemic refractory ventricular fibrillation, ST-segment elevation myocardial infarction, ventricular fibrillation