Alveolar Capillary Dysplasia with Misalignment of the Pulmonary Veins (ACDMPV) is a rare disorder, with only approximately 200 cases reported to date. The most common presentation of ACDMPV is hypoxic respiratory failure, a condition commonly encountered in preterm neonates. However, the clinical course of the hypoxic respiratory failure and unremitting pulmonary hypertension contrasts dramatically from the usual course of persistent pulmonary hypertension of the neonate (PPHN) in late preterm infants. A 35 4/7 week male infant was born via spontaneous vaginal delivery after routine resuscitation with APGARS of 8 and 8 at one and five minutes of life. Mild respiratory distress began at one hour of life resulting in initiation of CPAP. Chest radiograph demonstrated a small pneumothorax , which resolved spontaneously. Respiratory distress progressed on day of life two requiring increased FiO2 and escalation of respiratory support to endotracheal intubation and mechanical ventilation. Arterial blood gas performed at the time of intubation revealed a respiratory acidosis with a pH of 7.2 and PCO2 of 63, and hypoxemic respiratory failure with a pO2 of 26. Echocardiogram demonstrated normal intra-cardiac anatomy with severe pulmonary hypertension and right to left shunting across a large patent ductus arteriosus. Inhaled nitric oxide (iNO) therapy was initiated without improvement in pulmonary vascular pressures and the infant was transferred to a tertiary care center for evaluation for extracorporeal membrane oxygenation (ECMO) support as supportive management of PPHN. Following transport, the infant was cannulated to Venous-Arterial (V-A) ECMO day of life six, due to worsening lactic acidosis despite efforts to optimize oxygen delivery via blood pressure support, continued administration of iNO and transfusion of packed red blood cells. Full ECMO support was continued for four days, after a trial off of ECMO support revealed a pO2 of 69 on 40% FiO2. Over the next ten days, the infant had progressively worsening pulmonary hypertension leading to right ventricular failure and hypoxic respiratory failure. He was re-cannulated to V-A ECMO day of life 20. A lung biopsy performed during the second ECMO course provided the definitive diagnosis of ACDMPV. The infant was de-cannulated from VA- ECMO day of life 34 and died within three days. Many features of the clinical course of ACDMPV overlap with common disorders that result in PPHN in the neonatal period. Significantly, 94% of the of ACDMPV cases reported in the literature to date occur in term infants, thus the condition may be under-recognized and therefore under-diagnosed in this age group. This case illustrates the importance of consideration of the diagnosis of ACDMPV in preterm neonates, who following an uncomplicated delivery manifest progressive pulmonary hypertension and hypoxemic respiratory failure. Early identification of these patients can avoid excessive medical interventions and decrease emotional distress in families.