The 1994 American European Consensus Committee definitions of acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) have not been applied systematically in the pediatric population. The purpose of this study was to evaluate prospectively the epidemiology and clinical risk factors associated with death and prolonged mechanical ventilation in all pediatric patients admitted to two large, pediatric intensive care units with ALI/ARDS using Consensus criteria. All pediatric patients meeting Consensus Committee definitions for ALI were prospectively identified and included in a relational database. There were 328 admissions for ALI/ARDS with a mortality of 22%. Multivariate logistic regression analyses revealed (1) the initial severity of oxygenation defect, as measured by the Pa_O2/FI_O2 ratio; (2) the presence of nonpulmonary and non–central nervous system (CNS) organ dysfunction; and (3) the presence of CNS dysfunction were independently associated with mortality and prolonged mechanical ventilation. A substantial fraction of patients (28%) did not require mechanical ventilation at the onset of ALI; 46% of these patients eventually required intubation for worsening ALI. Mortality in pediatric ALI/ARDS is high and several risk factors have major prognostic value. In contrast to ALI/ARDS in adults, the initial severity of arterial hypoxemia in children correlates well with mortality. A significant fraction of patients with pediatric ALI/ARDS can be identified before endotracheal intubation is required. These patients provide a valuable group in whom new therapies can be tested.