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Background: A life-threatening complication of coronavirus disease 2019 (COVID-19) is acute respiratory distress syndrome (ARDS) refractory to conventional management. Venovenous (VV) extracorporeal membrane oxygenation (ECMO) (VV-ECMO) is used to support patients with ARDS in whom conventional management fails. Scoring systems to predict mortality in VV-ECMO remain unvalidated in COVID-19 ARDS. This report describes a large single-center experience with VV-ECMO in COVID-19 and assesses the utility of standard risk calculators., Methods: A retrospective review of a prospective database of all patients with COVID-19 who underwent VV-ECMO cannulation between March 15 and June 27, 2020 at a single academic center was performed. Demographic, clinical, and ECMO characteristics were collected. The primary outcome was in-hospital mortality; survivor and nonsurvivor cohorts were compared by using univariate and bivariate analyses., Results: Forty patients who had COVID-19 and underwent ECMO were identified. Of the 33 patients (82.5%) in whom ECMO had been discontinued at the time of analysis, 18 patients (54.5%) survived to hospital discharge, and 15 (45.5%) died during ECMO. Nonsurvivors presented with a statistically significant higher Prediction of Survival on ECMO Therapy (PRESET)-Score (mean ± SD, 8.33 ± 0.8 vs 6.17 ± 1.8; P = .001). The PRESET score demonstrated accurate mortality prediction. All patients with a PRESET-Score of 6 or lowers survived, and a score of 7 or higher was associated with a dramatic increase in mortality., Conclusions: These results suggest that favorable outcomes are possible in patients with COVID-19 who undergo ECMO at high-volume centers. This study demonstrated an association between the PRESET-Score and survival in patients with COVID-19 who underwent VV-ECMO. Standard risk calculators may aid in appropriate selection of patients with COVID-19 ARDS for ECMO., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)