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Cardiopulmonary physiology was assessed by Doppler echocardiography in neonates undergoing pre-ECMO evaluation for meconium aspiration syndrome, congenital diaphragmatic hernia, persistent fetal circulation, and sepsis, from March 1987 through July 1992 (n = 136). Percent survival by diagnosis was: meconium aspiration syndrome, 86%; persistent fetal circulation, 68%; congenital diaphragmatic hernia, 63%; sepsis, 33%. Survival odds by diagnosis predicted a better outcome for meconium aspiration syndrome than for congenital diaphragmatic hernia and sepsis, and a better outcome for persistent fetal circulation than for sepsis. Percent survival for right-to-left patent ductus arteriosus flow (PDA) was 56%; other patent ductus arteriosus flow was 84%. In multivariate analysis, percent survival in congenital diaphragmatic hernia and persistent fetal circulation patients with right-to-left PDA flow suggested a worse outcome (% survival right-to-left vs other: congenital diaphragmatic hernia, 13% vs 70%; persistent fetal circulation, 25% vs 85%), whereas percent survival did not appear to suggest the same in meconium aspiration syndrome or sepsis patients. Similar analysis in non-ECMO patients suggested a worse outcome with right-to-left PDA flow in patients with meconium aspiration syndrome and congenital diaphragmatic hernia. Right-to-left PDA flow, sepsis, and congenital diaphragmatic hernia were associated with a poorer ECMO outcome. Initial assessment of PDA flow helps predict ECMO outcome.