OBJECTIVES: To describe mechanical ventilation strategies in acute lung injury and to estimate the number of eligible patients for clinical trials on mechanical ventilation management. In contrast to adult medicine, there are few clinical trials to guide mechanical ventilation management in children with acute lung injury. DESIGN: A cross-sectional study for six 24-hr periods from June to November 2007. SETTING: Fifty-nine pediatric intensive care units in 12 countries in North America and Europe. PATIENTS: We identified children meeting acute lung injury criteria and collected detailed information on illness severity, mechanical ventilatory support, and use of adjunctive therapies. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 3823 patients screened, 414 (10.8%) were diagnosed with acute lung injury by their treating physician, but only 165 (4.3%) patients met prestablished inclusion/exclusion criteria to this trial and, therefore, would have been eligible for a clinical trial. Of these, 124 (75.2%) received conventional mechanical ventilation, 27 (16.4%) received high-frequency oscillatory ventilation, and 14 (8.5%) received noninvasive mechanical ventilation. In the conventional mechanical ventilation group, 43.5% were ventilated in a pressure control mode with a mean tidal volume of 8.3 +/- 3.3 mL/kg; and there was no clear relationship between positive end-expiratory pressure and Fio2 delivery in the conventional mechanical ventilation group. Use of adjunctive treatments, including nitric oxide, prone positioning, surfactant, hemofiltration, recruitment maneuvers, steroids, bronchodilators, and fluid restriction, was highly variable. CONCLUSIONS: Our study reveals inconsistent mechanical ventilation practice and use of adjunctive therapies in children with acute lung injury. Pediatric clinical trials assessing mechanical ventilation management are needed to generate evidence to optimize outcomes. We estimate that a large number of centers ( approximately 60) are needed to conduct such trials; it is imperative, therefore, to bring about international collaboration.