One hundred ten infants with congenital diaphragmatic hernia (CDH) developed life-threatening respiratory distress in the first 6 hours of life. Associated anomalies were present in 33%. Twenty-eight of 65 infants (43%) treated before 1987 (pre-extracorporeal membrane oxygenation [ECMO] era) survived after immediate CDH repair, and mechanical ventilation with or without pharmacologic support. Only two of 16 (12.5%) infants requiring a prosthetic diaphragmatic patch survived. Since 1987, 31 of 46 (67.4%) infants with birth weight, gestational age, and severity of illness similar to the pre-1987 group survived. All patients were immediately intubated and ventilated. Seven (four with lethal chromosomal anomalies) infants died before treatment, and 30 stabilized (partial pressure of carbon dioxide [PCO2] < 50; partial pressure of oxygen [PO2] > 100; pH > 7.3) and underwent delayed CDH repair at 5 to 72 hours. Fifteen did well on conventional support and survived. Fifteen infants deteriorated after operation: 11 were placed on ECMO with eight survivors, and four infants were not considered ECMO candidates. Nine babies failed to stabilize initially and were placed on ECMO before CDH repair (alveolar-arterial gradient > 600 and oxygenation index > 40), and seven survived. The overall survival rate was 80% at 3 months in this ECMO-treated group. Early mortality was due to inability to wean from ECMO (one), intracranial hemorrhage (one), liver injury (one), and pulmonary hypoplasia (one). Nine of 11 babies requiring a prosthetic patch in the post-1987 ECMO group survived (81.8%). There were three late post-ECMO deaths (3 to 18 months) of right heart failure (two) and sepsis (one). Symptomatic gastroesophageal reflux occurred in nine cases, six requiring a fundoplication in the bypass babies. Recurrent diaphragmatic hernia occurred in nine cases (five ECMO). The overall survival rate was significantly improved in the delayed repair/ECMO group (67% versus 43%; p < 0.05) and was most noticeable in infants requiring a prosthetic diaphragm (81.2% versus 12.5%; p < 0.005). These data indicate that early stabilization, delayed repair, and ECMO improve survival in high-risk CDH. Early deaths are related to pulmonary hypertension and can be reversed by ECMO.