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Introduction: Growing evidence supports extracorporeal cardiopulmonary resuscitation (ECPR) for refractory out-of-hospital cardiac arrest (OHCA) patients, especially in experienced centres. We present characteristics, treatments, and outcomes of patients treated with ECPR in a high-volume cardiac arrest centre in the metropolitan area of Milan, Italy and determine prognostic factors., Methods: Refractory OHCA patients treated with ECPR between 2013 and 2022 at IRCCS San Raffaele Scientific Institute in Milan had survival and neurological outcome assessed at hospital discharge., Results: Out of 307 consecutive OHCA patients treated with ECPR (95% witnessed, 66% shockable, low-flow 70 [IQR 58-81] minutes), 17% survived and 9.4% had favourable neurological outcome. Survival and favourable neurological outcome increased to 51% (OR = 8.7; 95% CI, 4.3-18) and 28% (OR = 6.3; 95% CI, 2.8-14) when initial rhythm was shockable and low-flow (time between CPR initiation and ROSC or ECMO flow) ≤60 minutes and decreased to 9.5% and 6.3% when low-flow exceeded 60 minutes (72% of patients). At multivariable analysis, shockable rhythm (aOR for survival = 2.39; 95% CI, 1.04-5.48), shorter low-flow (aOR = 0.95; 95% CI, 0.94-0.97), intermittent ROSC (aOR = 2.5; 95% CI, 1.2-5.6), and signs of life (aOR = 3.7; 95% CI, 1.5-8.7) were associated with better outcomes. Survival reached 10% after treating 104 patients ( p for trend <0.001)., Conclusions: Patients with initial shockable rhythm, intermittent ROSC, signs of life, and low-flow ≤60 minutes had higher success of ECPR for refractory OHCA. Favourable outcomes were possible beyond 60 minutes of low-flow, especially with concomitant favourable prognostic factors. Outcomes improved as the case-volume increased, supporting treatment in high-volume cardiac arrest centres., Competing Interests: TS is the Social Media Editor of Resuscitation Plus. All other authors declare they have no financial interests/personal relationships which may be considered as potential competing interests., (© 2023 The Authors.)