Pulmonary failure is the most frequent cause of mortality in newborns, accounting for 15,000 deaths yearly. It may be the result of the respiratory distress syndrome (RDS), meconium aspiration syndrome (MAS), or persistent fetal circulation (PFC) including infants with congenital diaphragmatic hernia (CDH). Early identification of patients with predictably fatal but potentially reversible respiratory failure refractory to conventional management protocols would permit orderly application of extracorporeal membrane oxygenation (ECMO) as a final resuscitative measure. Eight neonates with severe pulmonary failure manifested by A-a DO 2 of >620 torr for >12 hr, persistent cardiovascular instability, and relentless progression of acidosis and hypoxemia were predicted to have a 100% mortality in spite of maximal medical therapy. Four patients presented with MAS and 4 others had PFC, including 2 with CDH. All were supported with ECMO using the internal jugular vein and common carotid artery for access to the right atrium and aortic arch. Following support for 77–313 hr, 6 were successfully weaned from ECMO and then from the ventilator. In these few patients the use of extracorporeal membrane oxygenation after exhaustion of standard therapy was accomplished safely and successfully without untoward short-term sequelae. Extracorporeal ventilatory support may purchase the critical time necessary for resolution of the underlying parenchymal disease, including the pulmonary hypertension associated with CDH.