Our study objective was to assess health-related quality of life in survivors of acute lung injury (ALI) and to supplement generic and disease-specific questionnaires with findings from a focus group of ALI survivors. Six patients participated in the focus group, which revealed patient concerns with amnesia, depressed mood, avoidance behaviors, and a prolonged recovery period. Using a cross-sectional study design, 24 patients completed a questionnaire 6 to 41 mo after their lung injury. A total of 43% of the patients with ALI met criteria for depression; 43% had self-reported significant functional limitations, although 39% had minimal or no limitations. Significant respiratory and psychologic symptoms were reported in a quarter to a third of patients. There were large decrements in all domains of the SF-36 (a generic health-related quality-of-life instrument) in our sample compared with norms previously established for the general population. In addition, our patients had similar physical difficulties compared with previously studied patients with chronic medical illnesses but had more deficits in the social functioning and mental health domains. We conclude that long after lung injury, survivors have significantly lower health-related quality of life than the general population and are likely to have pulmonary and psychologic symptoms.