BackgroundA better understanding of the relative contributions of various factors to patient outcomes is essential for optimal patient selection for extracorporeal cardiopulmonary resuscitation (ECPR) therapy for patients with out-of-hospital cardiac arrest (OHCA). However, evidence on the prognostic comparison based on the etiologies of cardiac arrest is limited. Research QuestionWhat is the etiology-based prognosis of patients undergoing ECPR for OHCA? Study Design and MethodsThis retrospective multicenter registry study involved 36 institutions in Japan and included all adult patients with OHCA who underwent ECPR between January 2013 and December 2018. The primary etiology for OHCA was determined retrospectively from all hospital-based data at each institution. We performed a multivariable logistic regression model to determine the association between etiology of cardiac arrest and two outcomes: favorable neurological outcomes and survival at hospital discharge. ResultsWe identified 1,781 eligible patients, of whom 1,405 (78.9%) had cardiac arrest due to the cardiac causes. Multivariable logistic regression analysis for favorable neurological outcomes showed that accidental hypothermia (adjusted OR = 5.12; 95% CI = 2.98-8.80, P < 0.001) was associated with a significantly higher rate of favorable neurological outcomes than cardiac causes. Multivariable logistic regression analysis for survival showed that accidental hypothermia (adjusted OR = 5.19; 95% CI = 3.15-8.56, P < 0.001) had significantly higher rates of survival than cardiac causes. Acute aortic dissection/aneurysm (adjusted OR = 0.07, 95% CI = 0.02-0.28, P < 0.001) and primary cerebral disorders (adjusted OR = 0.12, 95% CI = 0.03-0.50, P = 0.004) had significantly lower rates of survival than cardiac causes. InterpretationIn this retrospective multicenter cohort study, although most OHCA patients underwent ECPR for cardiac causes, accidental hypothermia was associated with favorable neurological outcomes and survival; in contrast, acute aortic dissection/aneurysm and primary cerebral disorders were associated with non-survival than cardiac causes.