In the initial phases of veno-venous extracorporeal membrane oxygenation (VV ECMO) support for severe acute respiratory distress syndrome (ARDS), ultraprotective controlled mechanical ventilation (CMV) is typically employed to limit the progression of lung injury. As patients recover, transitioning to assisted mechanical ventilation can be considered to reduce the need for prolonged sedation and paralysis. This study aimed to evaluate the feasibility of transitioning to pressure support ventilation (PSV) during VV ECMO and to explore variations in respiratory mechanics and oxygenation parameters following the transition to PSV. This retrospective monocentric study included 191 adult ARDS patients treated with VV ECMO between 2009 and 2022. Within this population, 131 (69%) patients were successfully switched to PSV during ECMO. Pressure support ventilation was associated with an increase in respiratory system compliance (p = 0.02) and a reduction in pulmonary shunt fraction (p < 0.001). Additionally, improvements in the cardiovascular Sequential Organ Failure Assessment score and a reduction in pulmonary arterial pressures (p < 0.05) were recorded. Ninety-four percent of patients who successfully transitioned to PSV were weaned from ECMO, and 118 (90%) were discharged alive from the intensive care unit (ICU). Of those who did not reach PSV, 74% died on ECMO, whereas the remaining patients were successfully weaned from extracorporeal support. In conclusion, PSV is feasible during VV ECMO and potentially correlates with improvements in respiratory function and hemodynamics.