When clinicians consider extracorporeal life support (ECLS) for acute respiratory distress syndrome (ARDS) patients with hemodynamic instability, both veno-arterial (VA) and veno-venous (VV) ECLS are therapeutic possibilities. We analyzed 17 patients with ARDS on inotropic or vasopressor support requiring ECLS for refractory hypoxemia. After implementing VV ECLS, pressor requirements (based on norepinephrine equivalents) were significantly lower in all patients (P = .0001 for overall comparison across time points). None of the 17 patients required conversion from VV ECLS to VA ECLS (95% confidence interval 0%–20.0%). In this sample of 17 patients with substantial baseline vasopressor support and hypoxemic respiratory failure, initiation of VV ECLS was associated with reduced pressor requirements. Such a strategy may help avoid complications of VA ECLS in patients with both respiratory and hemodynamic failure.