The hepatopulmonary syndrome (HPS), consisting of elevated alveolar-arterial oxygen gradient and intrapulmonary vascular abnormalities in the presence of advanced liver disease, is associated with high mortality. Liver transplantation (LT) has been used for the treatment of HPS; however, the success of LT for the treatment of HPS is not uniformly documented. We reviewed our experience over a 5-year period and identified eight adult patients with incapacitating respiratory symptoms compatible with HPS. Inclusion criteria included hypoxemia, normal lung volumes, reduced oxygen diffusing capacity (D(L)CO), and the presence of intrapulmonary shunting. Underlying liver disease was caused by hepatitis C (2 patients), primary biliary cirrhosis (1 patient), cryptogenic cirrhosis (1 patient), alcohol (2 patients), and hepatitis C with alcohol (2 patients). Six out of eight patients required preoperative oxygen support. Severe hypoxemia was present in seven patients (Pa(O2) 51.5 +/- 8.2 mm Hg). Three patients had complicating pulmonary hypertension. All patients exhibited a severely reduced D(L)CO (44.6 +/- 12.2% of predicted value). Six patients were transplanted, with five requiring oxygen support at the time of discharge. Resolution of oxygen dependency occurred in all patients but was delayed in the two patients exhibiting complicating pulmonary hypertension (288.5 +/- 37.4 v 53.5 +/- 35.7 days). All patients exhibited O2 saturations greater than 98% on room air. Currently, three patients are alive and off oxygen. The current report documents successful resolution of hypoxemia after LT in this pilot cohort. This supports the newly implemented United Network for Organ Sharing (UNOS) criteria, that LT for HPS may be extended to include patients with Pa(O2) < 60 mm Hg.