OBJECTIVE: To synthesize the emerging body of experimental, observational, and clinical trial data into a practical guideline for safe and effective ventilatory management of acute respiratory distress syndrome. DATA SOURCES: Relevant, peer-reviewed, scientific literature and personal observations from clinical practice. STUDY SELECTION: Relevant experimental studies and high-impact observational and clinical trials of acute respiratory distress syndrome management. DATA EXTRACTION: Detailed review of information contained in published scientific work. DATA SYNTHESIS: Interactive discussions between the authors that culminated in our consensus view of appropriate management. CONCLUSIONS: Prevention of ventilator-induced lung injury while accomplishing the essential life-supporting roles of mechanical ventilation is a complex undertaking that requires application of principles founded on a broad experimental and clinical database and on the results of well-executed clinical trials. At the bedside, execution of an effective lung-protective ventilation strategy remains an empirical process best guided by integrated physiology and a readiness to revise the management approach depending on the individual's response.