BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a complex procedure of life support in severe but potentially reversible respiratory failure, used particularly in mature newborn infants. Although the number of babies requiring ECMO is small, and the ECMO policy invasive and potentially expensive, its benefits may be high. OBJECTIVES: To determine whether ECMO used for neonatal infants with severe respiratory failure is clinically effective and cost-effective compared to a policy of conventional ventilatory support. SEARCH STRATEGY: The Cochrane Neonatal Group Specialised Register, the Cochrane Controlled Trials Register, and MEDLINE were searched for 1974 to 2001. SELECTION CRITERIA: All randomised trials comparing neonatal ECMO to conventional ventilatory support. DATA COLLECTION AND ANALYSIS: The authors independently evaluated the trials for methodological quality and appropriateness for inclusion in the Review (without consideration of their results), and then independently extracted the data. MAIN RESULTS: The three trials from the USA and one from the UK recruited clinically similar groups of babies. Two trials excluded infants with congenital diaphragmatic hernias. In two, transfer for ECMO implied transport over a considerable distance. One study included an economic evaluation. Two trials had follow up information. All except the UK trial had very small numbers of patients. Two of the trials used conventional randomisation with low potential for bias. The other two used less usual designs which have led to difficulties in their interpretation. All four trials showed a strong benefit of ECMO on mortality (RR 0.44; 95% CI 0.31 to 0.61), especially for babies without congenital diaphragmatic hernia (RR 0.33, 95% CI 0.21 to 0.53). Only the UK trial provided information about death or disability at one and four years, and showed benefit of ECMO at one year (RR 0.56, 95% CI 0.40 to 0.78), and at four years (RR 0.62, 95% CI 0.45 to 0.86). Overall nearly half of the children had died or were severely disabled at four years of age, reflecting the severity of their underlying conditions. Based on economic analysis from the UK trial, the ECMO policy is as cost-effective as other intensive care technologies in common use. REVIEWER'S CONCLUSIONS: A policy of using ECMO in mature infants with severe but potentially reversible respiratory failure would result in significantly improved survival without increased risk of severe disability amongst survivors. For babies with diaphragmatic hernia ECMO offers short term benefits but the overall effect of employing ECMO in this group is not clear. Further studies are needed to refine ECMO techniques; to consider the optimal timing for introducing ECMO; to identify which infants are most likely to benefit; and to address the longer term implications of neonatal ECMO during later childhood and adult life.