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Background: In March 2020, COVID-19 was announced as a global pandemic. The first COVID-19 patient was connected to an ECMO device in Israel during that time. Since then, over 200 patients have required ECMO support due to COVID-19 infection. The present study is a multi-institutional analysis of all COVID-19 patients requiring veno-venous (VV) ECMO in Israel. The aim was to characterize and compare the survivors and deceased patients as well as establish risk factors for mortality. Methods: This retrospective multi-institutional study was conducted from March 2020 to March 2021 in eleven of twelve ECMO centers operating in Israel. All COVID-19 patients on VV ECMO support were included in the cohort. The patients were analyzed based on their comorbidities, procedural data, adverse event on ECMO, and outcomes. Univariate and multivariate analyses were used to compare the deceased and the surviving patients. Results: The study included 197 patients, of which 150 (76%) were males, and the mean age was 50.7 ± 12 years. Overall mortality was 106 (54%). Compared with the deceased subjects, survivors were significantly younger (48 ± 11 vs. 53 ± 12 years), suffered less from ischemic heart disease (IHD) (3% vs. 12%), and were ventilated for a significantly shorter period (≤4 days) prior to cannulation (77% vs. 63%). Patients in the deceased group experienced more kidney failure and sepsis. Rates of other complications were comparable between groups. Conclusions: Based on this study, we conclude that early cannulation (≤4 days) of younger patients (≤55 years) may improve overall survival and that a history of IHD might indicate a reduced prognosis.