OBJECTIVE: To analyze the impact of the modification of the authors' institutional protocol on outcomes after extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest (OHCA). DESIGN: An observational analysis. The protocol complied with national recommendations. A further eligibility criterion was added since January 2015: the presence of sustained shockable rhythm at extracorporeal life support (ECLS) implantation. To assess the impact of this change, patients were divided into two groups: (1) from January 2010 to December 2014 (group A) and (2) from January 2015 to December 2019 (group B). The primary endpoint was survival to hospital discharge with good neurologic outcome. Predictors of survival were searched with multivariate analyses. SETTING: University hospital. PARTICIPANTS: Adult patients supported with ECPR for refractory OHCA. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: From January 2010 to December 2019, 85 patients had ECLS for OHCA (group A, n = 68, 80%; group B, n = 17, 20%). The mean age was 42.4 years, 78.8% were male. The rate of implantation of ECLS was significantly lower in group B (p = 0.01). Mortality during ECLS support was significantly lower (58.8 v 86.8%; p = 0.008), and the weaning rate was significantly higher (41.2 v 13.2%; p = 0.008) in group B. Survival to discharge with good neurologic outcome was significantly improved (23.5 v 4.4%; p = 0.027) in group B. A sustained shockable rhythm was the only independent predictor of survival to hospital discharge with good neurologic outcome. CONCLUSIONS: The modification of the authors' institutional protocol throughout the further criterion of sustained shockable rhythm yielded a favorable impact on outcomes after ECPR for OHCA.