Objectives: The respiratory workload, according to the diaphragm thickening fraction (TF) during sweep gas flow (SGF), decrease during weaning from venoarterial extracorporeal membrane oxygenation (VA ECMO) was evaluated for the present study. Design: Prospective observational study. Setting: Monocentric. Participants: Patients were included if they were suitable for a first VA ECMO weaning trial and were breathing spontaneously. Interventions: SGF was set for 15 minutes when the TF was measured at 4 L/min, 2 L/min, and 1 L/min, with a 10-minute return to baseline between each step. Mechanical ventilation, when required, was set to pressure-support ventilation mode with 7 cmH2O (pressure support) and a positive end-expiratory pressure of 0 cmH2O. Diaphragm ultrasound was used to assess the TF at the end of each step. Demographics, left ventricular ejection fraction (LVEF), and outcome were collected. Measurements and main results: Fifteen patients were included. Ten patients were extubated, and five were ventilated. TF values were 6.3% [0-10] at 4 L/min, 13.3% [10-26] at 2 L/min, and 26.7% [22-44] at 1 L/min (analysis of variance: p < 0.001 between 4 L/min and 2 L/min and p = 0.03 between 2 L/min and 1 L/min). TF did not differ whether patients were or were not ventilated or whether they were or were not weaned successfully from ECMO. TF was correlated with LVEF at 1 L/min SGF (Pearson R 0.67 [0.21-0.88]; p = 0.009) and at 2 L/min (R 0.7 [0.27-0.89]; p = 0.005) but not at 4 L/min. SGF mitigated the relationship between LVEF and TF (analysis of covariance: p < 0.005). Conclusions: Diaphragm TF was related to the SGF of the venoarterial ECMO settings and LVEF at the time of weaning.