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BACKGROUND Extubation strategy in extracorporeal life support patients remains unclear, and literature only reports studies with significant biases. OBJECTIVES To explore the prognostic impact of an early ventilator-weaning strategy in assisted patients after controlling for confounding factors. METHODS A 10-year retrospective study included 241 patients receiving extracorporeal life support for at least 48 hours, corresponding to a total of 977 days spent on assistance. The a priori probability of extubation for each day of assistance was calculated according to daily biological examinations, drug doses, clinical observations and admission data to pair each day containing an extubation with one on which the patient was not extubated. The primary outcome was survival at day 28. The secondary outcomes were survival at day 7, respiratory infections and safety criteria. RESULTS Two similar cohorts of 61 patients were generated. Survival at day 28 was better in patients extubated under assistance in univariate and multivariate (HR=0.37[0.2-0.68], p-value=0.002) analyses. Patients who underwent failed early extubation did not have a different prognosis from those without early extubation. Successful early extubation was associated with a better outcome than a failed or no attempt at early extubation. Survival at day 7 and the rate of respiratory infections were better in early-extubated patients. Safety data did not differ between the two groups. CONCLUSIONS Early extubation during assistance was associated with a superior outcome in our propensity-matched cohort study. The safety data were reassuring. However, due to the lack of prospective randomized studies, the causality remains uncertain.