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To assess the impact of implementing a low tidal volume ventilation strategy on hospital mortality for patients with acute lung injury or acute respiratory distress syndrome.Retrospective, uncontrolled study.Adult medical-surgical and trauma intensive care units at a major inner city, university-affiliated hospital.A total of 292 patients with acute lung injury or acute respiratory distress syndrome.Between the years 2000 and 2003, 200 prospectively identified patients with acute lung injury/acute respiratory distress syndrome were managed by the ARDS Network low tidal volume protocol. A historical control group of 92 acute respiratory distress syndrome patients managed by routine practice from 1998 to 1999 was used for comparison.Patients managed with the ARDS Network protocol had a lower hospital mortality compared with historical controls (32% vs. 51%, respectively; p = .004). Multivariate logistic regression estimated an odds ratio of 0.32 (95% CI, 0.17–0.59; p = .0003) for mortality risk with use of the ARDS Network protocol. Protocol-managed patients had a lower tidal volume (6.2 ± 1.1 vs. 9.8 ± 1.5 mL/kg; p < .0001) and plateau pressure (27.5 ± 6.4 vs. 33.8 ± 8.9 cm H2O; p < .0001) than historical controls.Adoption of the ARDS Network protocol for routine ventilator management of acute lung injury/acute respiratory distress syndrome patients was associated with a lower mortality compared with recent historical controls.