RATIONALE: Whether a nurse-implemented goal-directed sedation protocol resulting in more awake yet calm intubated children affects post-discharge functional status, health-related quality of life, or risk for post-traumatic stress disorder is unknown. OBJECTIVES: To compare post-discharge outcomes in children with acute respiratory failure cluster randomized to a sedation protocol or usual care. METHODS: A stratified random sample of 1360 patients from 31 centers in the Randomized Evaluation of Sedation Titration for Respiratory Failure trial was assessed by mail, electronically, and/or telephone six months after intensive care unit discharge. In treatment group comparisons, we controlled for age, baseline functional status, and severity of illness. MEASUREMENTS AND MAIN RESULTS: We used the Pediatric Overall and Cerebral Performance categories to characterize functional status, the Infant and Toddler Quality of Life Questionnaire-97 (<2 years old) or Pediatric Quality of Life Inventory (>/=2 years old), and the Child Post-traumatic Stress Disorder Symptom Scale (>/=8 years old and developmentally able). Functional status worsened from baseline to follow-up in 20%. Decline in functional status did not differ by treatment arm and was more common among those with baseline impairment than those with baseline normal function (27% vs. 18%; P<0.001). There were no significant differences in health-related quality of life total scores by treatment arm. Scores indicating risk of post-traumatic stress disorder occurred in 30%, with no difference between treatment arms. CONCLUSIONS: A sedation strategy that allows patients to be more awake and exposes them to fewer sedative and analgesic medications produces no long-term harm. However, post-discharge morbidity after acute respiratory failure is common. Clinical trial registration available at www.clinicaltrials.gov, ID NCT00814099.