Persistent pulmonary hypertension is an important cause of mortality and morbidity in term infants. The lung assist device (LAD) is a novel, pumpless, low-resistance extracorporeal oxygenator to supplement mechanical ventilation. The LAD may be associated with fewer complications compared with conventional extracorporeal membrane oxygenation. The objective was to test the feasibility and efficacy of the LAD in juvenile piglets with hypoxia-induced pulmonary hypertension. Pulmonary hypertension was acutely induced by hypoxia in six 3-to 4-wk-old acutely instrumented and intubated piglets. The LAD was attached between a carotid artery and jugular vein. Gas exchange and hemodynamic variables, including pulmonary arterial pressure (PAP) and cardiac output (CO), were measured. Successful LAD cannulation was achieved without complications in all animals. Extracorporeal shunt flow through the device averaged 18% of CO. The LAD achieved oxygen delivery of 20% of total oxygen consumption. PAP was reduced by 35% from 28 ± 5 to 18 ± 4 mm Hg (p < 0.05) and systemic Pao2 increased by 33% from 27 ± 2 to 36 ± 4 mm Hg (p < 0.05). Other hemodynamic variables remained stable. The novel LAD shows feasibility and efficacy in improving gas exchange and reducing PAPs in a juvenile animal model of hypoxia-induced pulmonary hypertension. © 2009 International Pediatric Research Foundation, Inc.