Despite the introduction of new ventilation techniques and surfactant therapy, some premature infants still experience severe respiratory failure and either die or survive with severe bronchopulmonary dysplasia. Extracorporeal membrane oxygenation is currently not offered for preterm infants with a birth weight less than 2,000 g, mainly because of the potential high risk for intracranial hemorrhage. The aim of this study was to determine risk predictors for mortality alone and for mortality or major lung morbidity in 1,500–1,999 g premature infants with respiratory failure. We reviewed the medical records of all preterm infants (n = 459) with respiratory failure and a birth weight of 1,500–1,999 g treated at five medical centers from 1989 to 1991. Of those infants, 23 (5%) had severe respiratory failure, defined as a requirement for ventilatory support with the fraction of inspired oxygen ≥ 0.8 or peak inspiratory pressure ≥ 30 cmH2O for ≥ 3 hr in the 1st week of life. A mortality of ≥ 75% was associated with a single arterial/alveolar oxygen ratio ≤ 0.04; pulmonary air leak alone or pulmonary air leak with a mean airway pressure ≥ 12 cmH2O; and arterial oxygen tension ≤ 50 mmHg. These risk predictors may provide a basis for the selection of patients for future clinical trials of extracorporeal membrane oxygenation in this high-risk group of 1,500–1,999 g premature infants with severe respiratory failure.