Rationale: In a clinical trial by the Acute Respiratory Distress Syndrome Network (ARDSNet), mechanical ventilation with tidal volumes of 6 ml/kg decreased mortality from acute lung injury. However, interpretations of these results generated controversy and it was unclear if this trial would change usual care practices. Objectives: First, to determine if clinical practices at ARDSNet hospitals changed after the tidal volume trial. Second, to determine if tidal volume (V_T) and plateau pressure (Pplat) within 48 hours before randomization affected hospital mortality in patients subsequently managed with 6 ml/kg PBW (predicted body weight). Methods: We used pre-enrollment data from 2,451 patients enrolled in six trials (1996-2005) to describe changes in V_T over time. We used logistic regression to determine if pre-enrollment V_T or Pplat affected mortality. Results: Median pre-enrollment V_T decreased from 10.3 ml/kg PBW (range 4.3-17.1) during the tidal volume trial (1996-1999) to 7.3 ml/kg PBW (range 3.9-16.2) after its completion (p-value<0.001). Pre-enrollment V_T was not associated with mortality (pvalue= 0.566). The odds of death increased multiplicatively with each cm H₂O of preenrollment Pplat (p-value<0.001), e.g., the odds of death was 1.37 times greater when pre-enrollment Pplat increased by 10 cm H₂O. Conclusions: Physicians used lower tidal volumes after publication of the tidal volume trial. Pre-enrollment plateau pressure was strongly associated with mortality, and may reflect disease severity independent of tidal volume. Plateau pressure measured early in the course of acute lung injury, after accounting for tidal volume, is a respiratory systemspecific value with strong prognostic significance.