Objectives:To determine the effect of a ventilation strategy to prevent barotrauma on long-term outcome in survivors of acute lung injury.Design:Prospective blinded cohort analysis.Setting:Three university-affiliated medical-surgical intensive care units.Patients:A total of 28 survivors of acute lung injury, 1-2 yrs after diagnosis, from a multicenter prospective randomized controlled trial comparing pressure (peak inflation pressure ≤30 cm H2O) and volume (tidal volume ≤8 mL/kg) limited ventilation to a conventional (peak inflation pressure ≤50 cm H2O, tidal volume 10-15 mL/kg) ventilation strategy.Measurements and Main Results:Physicians blinded as to treatment group evaluated 20 of 28 survivors (treatment group, 7; control group, 13). Exercise tolerance in the 6-minute walk test was comparable to patients with chronic respiratory disease and equivalent between groups (treatment group, 373 ± 171 m vs. control group, 375 ± 129 m;p= .84). Pulmonary function testing showed reduced diffusing capacity (treatment group, 64 ± 29% predicted vs. control group, 74 ± 14% predicted;p= .68) and normal volumes, flows, and blood gases. Two domains of disease-specific Health Related Quality of Life assessed by the Chronic Respiratory Questionnaire were worse for patients in the treatment group compared with the control group (Emotional Function 3.8 ± 1.4 vs. 5.1 ± 0.08;p= .05, Mastery 4.7 ± 1.7 vs. 6.2 ± 0.8;p= .03). There were no between-group differences in the scores of the Spitzer Quality of Life Index (a generic Health Related Quality of Life instrument), although they were reduced (7.5 ± 1.9) and comparable to patients with chronic disease.Conclusions:We found that 1-2 yrs after the onset of their illness, survivors of acute lung injury have reductions in quality of life and exercise tolerance which are similar to patients with chronic diseases. We were unable to show that a limited ventilation strategy improves either long-term pulmonary function or quality of life in survivors of acute lung injury.