Extracorporeal membrane oxygenation (ECMO) has rescued moribund infants with respiratory failure from a variety of causes. We report the experience from 58 United States and 7 overseas ECMO centers between 1980 and 1989. Voluntarily submitted data forms provided details of diagnosis, clinical condition, ECMO indications, morbidity, and mortality. Of 3,528 infants with a predicted mortality greater than 80% treated with ECMO, 83% survived. Entry diagnoses and aggregate survival were: meconium aspiration syndrome (MAS) 1,356 (93%), persistent pulmonary hypertension of the newborn (PPHN) 480 (83%); congenital diaphragmatic hernia (CDH) 585 (62%); hyaline membrane disease (HMD) 532 (84%); sepsis 416 (77%); and other 185 (77%). ECMO indications were a-AdO2 greater than 600 for 6 to 8 hours (22%), oxygenation index greater than 40 for 4 hours (18%), acute deterioration (14%), maximal therapy failure (34%), and barotrauma (1%). Annual survival improved over 9 years except for CDH, which decreased from 70% (1987) to 56% (1989) P less than .01). Survivors differed from non-survivors (P less than .05) by birth weight (greater than 2 kg), gestational age (greater than 37 weeks), entry diagnosis (MAS, PPHN, HMD, sepsis v CDH), inborn versus outborn, pre-ECMO pH, and ECMO duration. Technical complications in 25% of patients and medical complications in 75% adversely affected survival. Annual sepsis survival improved to 75% (1989) but had significantly greater complication rates (P less than .05) than other diagnoses. Multicenter data yield information not available from single institution experience. Although entry criteria and conventional therapy continue to evolve, ECMO currently improves survival from an estimated 20% to 83% overall. Individual prognosis depends on entry diagnosis, clinical condition, and complications.