Hepatopulmonary syndrome (HPS) is defined as hypoxemia induced by intrapulmonary vascular dilations associated with liver disease. Although liver transplantation (LT) is the only effective therapy established for severe HPS, patients with a partial pressure of arterial oxygen (PaO(2)) less than 60 mm Hg have a poor prognosis. We treated a 4-year-old boy with HPS whose preoperative PaO(2) level was 48.8 mm Hg. After LT, he had persistent severe hypoxemia, although he was receiving high-flow oxygen. Noninvasive ventilation (NIV) was introduced, and his respiratory insufficiency promptly improved. Therefore, NIV therapy immediately after extubation following transplantation was administered to the next 4 consecutive HPS patients whose preoperative PaO(2) was less than 60 mm Hg. The NIV treatment of these 5 patients could have been responsible for preventing severe postoperative complications as well as reintubation and hospital death. NIV therapy for both pediatric and adult patients with severe HPS immediately after extubation might protect them from severe hypoxemia after transplantation and from complications necessitating reintubation and might improve their prognosis. Liver Transpl 17:144-148, 2011. (C) 2011 AASLD.