Major malformations, surgery and persistent pulmonary hypertension (PHT) have been considered contraindications to therapeutic hypothermia (TH) in newborns with hypoxic-ischemic encephalopathy (HIE). We report two patients with undiagnosed congenital diaphragmatic hernia (CDH) who developed HIE after birth. Diagnosis of moderate HIE was formulated based on clinical, laboratory and electroencephalographic criteria. The patients were treated with whole body hypothermia (33.5 °C) for 72 h. During hypothermia the patients underwent surgical repair with regular perioperative course. Ventilatory support with high-frequency oscillatory ventilation, oxygen requirements and inotropic support remained stable during hypothermia. Serial echocardiographic evaluations did not demonstrate any change in pulmonary pressure values. In our experience TH did not increase the risk of hemodynamic instability, PHT or bleeding. Hypothermia may be considered in patients with HIE and CDH or other surgical conditions with favorable prognosis.