Abstract Funding Acknowledgements Type of funding sources: None. Introduction Refractory cardiac arrest, defined as the absence of sustained return of spontaneous circulation (ROSC) despite advanced life support (ALS), remains common and is burden by poor outcome. The Extracorporeal Cardiopulmonary Resuscitation (E-CPR) may benefit organ perfusion, potentially improving OHCA outcomes. Purpose The aim of this study was to evaluate outcome of patients with refractory OHCA managed with E-CPR. Methods Single centre prospective observational registry of all patients with OHCA treated with E-CPR from 1 September 2017 to 28 February 2021. The enrolment to E-CPR was defined according to hospital protocol. Results We enrolled 166 patients with OHCA. Out of 59, 39 cases (66,1%) were included in E-CPR program. Prevalence of shockable rhythms was 59%. Survival at discharge from ICU was 10,2% (4 patients; 3 of them discharged with CPC 1-2 and all with ventricular fibrillation at presentation). E-CPR versus patients without refractory arrest have been compared: patients in the E-CPR group were younger (p=0,0002), had lower mean arterial pressure at ROSC and higher SOFA score (p<0,0001). NSE values between survivor (53,8 ± 17,9 mcg/L) and non-survivor (104,8 ± 44,2 mcg/L) at 24 hours were statistically significant (p=0,0669) as well as lactate clearance in the first 48 hours (p=0,001). In the univariate regression model serum lactate at admission (p<0,001; 95% CI 0,87 to 6,83), longer low flow time (p<0,002; 95% CI 0,99 to 1,29) and lower mean arterial pressure (p<0,01; 95% CI 0,99 to 1,29) were associated to mortality. Whereas only lactates (p<0,001; 95% CI 0,092 to 4,56) and low flow time (p<0,001; 95% CI 0,092 to 0,17) retained the association in the multivariate model (figure 1 for ROC curves). Conclusion Mortality rate in OHCA remains unacceptably high. Patients undertaking E-CPR have worsen hemodynamic and clinical parameters at admission, likely to consequence of refractory cardiac arrest. Low-flow time and lactates level are related to higher mortality as expression of worsen metabolic condition related to hypoperfusion state in patients with delayed ROSC.