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The purpose of the study is to compare outcomes in patients who had severe hypoxemic respiratory failure (Pao2/fraction of inspired oxygen < 100) who received early veno-venous extracorporeal membrane oxygenation (ECMO) as an adjunct to mechanical ventilation, to those in patients who received conventional mechanical ventilation alone.This is a multicenter, retrospective unmatched and matched cohort study of patients admitted between April 2006 and December 2013. Generalized logistic mixed-effects models and Cox proportional hazards models were used to determine the association between treatment with ECMO that was started within 3 days of intensive care unit (ICU) admission and ICU and hospital mortality and length of stay, respectively.A total of 2440 patients who had severe hypoxemic respiratory failure due to various etiologies were included, 46 who received early veno-venous ECMO and 2394 unmatched and 398 matched controls who received conventional ventilation alone. Compared to matched controls, ECMO was associated with a lower odds of ICU (odds ratio [95% confidence interval], 0.30 [0.13–0.67]) and inhospital death (odds ratio 0.30 [0.14–0.67]). In addition, ECMO was associated with longer times to discharge from ICU and hospital (hazard ratio, 0.42 [0.37–0.47] and 0.53 [0.38–0.73], respectively).In this observational study, use of early ECMO compared to conventional mechanical ventilation alone in patients who had severe hypoxemic respiratory failure was associated with a lower risk of mortality and a longer length of stay.