ObjectiveTo determine the outcome and health-related quality of life of patients requiring ≥14 days of mechanical ventilation in the intensive care unit (ICU).DesignProspective cohort study with post-ICU, cross-sectional, health-related quality-of-life survey.SettingA 17-bed ICU in a university hospital.PatientsA consecutive cohort of 347 patients receiving mechanical ventilation for ≥14 days.InterventionsNone.Measurements and Main ResultsOf the patients enrolled in the study, 150 (44%) died in the ICU and 197 were discharged (58 of 197 died 1–57 months after discharge). Factors associated with ICU death according to multivariate logistic regression analysis were age ≥65 yrs, preadmission New York Heart Association functional class of ≥3, a preadmission immunocompromised status, septic shock at ICU admission, renal replacement therapy in the ICU, and nosocomial septicemia. Cox proportional hazards multivariate analysis identified age of ≥65, a preadmission immunocompromised status, and duration of mechanical ventilation for >35 days as independent predictors of death after ICU discharge. By contrast, postcardiac surgery patients had a better outcome. Health-related quality of life was evaluated for 87 of the 99 long-term survivors after a median follow-up of 3 yrs by using the Nottingham Health Profile and St. George’s Respiratory questionnaires. Compared with those of a general French population, their scores were significantly worse for each of the Nottingham Health Profile domains, except social isolation. Nottingham Health Profile scores did not significantly differ between postcardiac and nonpostcardiac surgery patients, men and women (except that women felt more socially isolated), and patients with and without acute respiratory distress syndrome (except for more sleep disorders in those with acute respiratory distress syndrome). Finally, pulmonary-specific St. George’s Respiratory Questionnaire global score was worse for acute respiratory distress syndrome survivors.ConclusionsProlonged mechanical ventilation is associated with impaired health-related quality of life compared with that of a matched general population. Despite these handicaps, 99% of the patients evaluated were independent and living at home 3 yrs after ICU discharge. Future studies should focus on physical or psychosocial rehabilitation that could lead to improved management of patients after their ICU stay.