Less than optimal outcomes for hypoplastic left heart syndrome may be related to unstable in-parallel circulation. Mechanical lung assist by (1) superior vena cava to right atrium pump with oxygenation (oxygenator assist), or (2) superior vena cava to pulmonary artery pump (pump assist) may permit successful neonatal in-series palliation. Nineteen 15-day-old piglets underwent single ventricle and bidirectional cavopulmonary shunt (BCPC) creation without mechanical lung assist (n = 8), with pump assist (n = 5), or with oxygenator assist (n = 6). Baseline hemodynamic measurements were not different between groups. Median survival for the cavopulmonary shunt alone, pump assist, and oxygenator assist groups was 28, 180, and 180 minutes, respectively (p = 0.0006). No differences in arterial oxygen concentration or bicarbonate levels were detected. Arterial carbon dioxide (p < or = 0.007) was higher in the cavopulmonary shunt alone versus lung assist groups. Cavopulmonary shunt alone animals had decreased mean arterial pressure (p < 0.02) and cerebral perfusion pressure (p = 0.029) and elevated left atrial pressure compared with lung assist groups (p < 0.05). This data demonstrates creation of a novel translational neonatal BCPC model in which mechanical lung assist augments survival. Early BCPC death was related to poor ventricular function and an inability to ventilate, issues that were improved with both types of lung assist.