In neonates with pulmonary hypertension (PH) supported on veno-venous extracorporeal membrane oxygenation (VV-ECMO), keeping the ductus arteriosus (DA) open ensures a high cardiac output of well-oxygenated blood through the right to left (R-L) ductal shunt. After PH resolution, timely closure of the patent DA (PDA) prevents pulmonary overcirculation, systemic hypoperfusion, and unsuccessful ECMO weaning. We retrospectively evaluated its impact on the echocardiographic and hemodynamic features of 18 newborns undergoing VV-ECMO because of acute hypoxic respiratory failure in PH. At ECMO start, PDA was left or maintained open for all patients with echocardiographic signs of PH. After ECMO initiation, PDA shunt reverted into left to right (L-R). Twenty-four hours before DA closure, the echocardiographic assessment suggested a drop in pulmonary vascular resistances (PVRs). At 24 and 48 hours after DA closure, cardiac ultrasound confirmed continued improvement of PH. Ductus arteriosus closure is associated with a significant drop in arterial lactates (p = 0.014) and increase in diastolic blood pressure (p = 0.037). All patients, except for the two who died on ECMO, were successfully weaned from extracorporeal life support. Overall survival was 61.1%. These preliminary data suggest the feasibility and safety of DA patency manipulation in neonates undergoing VV-ECMO for PH, supporting a VV configuration in this patient population.