In this quantitative systematic review we assessed the effects of ventilation with smaller tidal volume (VT) on morbidity and mortality in patients aged 16 yr or older affected by acute lung injury and acute respiratory distress syndrome. Five randomized trials (1202 patients) comparing ventilation using smaller VT and/or low airway driving pressure (plateau pressure 30 cm H2O or less), resulting in VT of 7 mL/kg or less versus ventilation that uses VT in the range of 10 to 15 mL/kg, were identified after a systematic search of The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, databases of current research, reference lists, and "gray literature." Mortality at day 28 was significantly reduced by lung-protective ventilation (relative risk [RR], 0.74; confidence interval [CI], 0.61-0.88), whereas beneficial effect on long-term mortality was uncertain (RR, 0.84; CI, 0.68-1.05). The comparison between small and conventional VT was not significantly different if a plateau pressure less than or equal to 31 cm H2O in the control group was used (RR, 1.13; CI, 0.88-1.45). Clinical heterogeneity, such as different lengths of follow-up and higher plateau pressures in control arms in two trials, make the interpretation of the combined results difficult.