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Decades-old, common ICU practices including deep sedation, immobilization, and limited family access are being challenged. We endeavoured to evaluate the relationship between ABCDEF bundle performance and patient-centered outcomes in critical care.Prospective, multicenter, cohort study from a national quality improvement collaborative.68 academic, community, and federal ICUs collected data during a 20-month period.15,226 adults with at least one ICU day.We defined ABCDEF bundle performance (our main exposure) in two ways: 1) complete performance (patient received every eligible bundle element on any given day) and 2) proportional performance (percentage of eligible bundle elements performed on any given day). We explored the association between complete and proportional ABCDEF bundle performance and three sets of outcomes: patient-related (mortality, ICU and hospital discharge), symptom-related (mechanical ventilation, coma, delirium, pain, restraint use), and system-related (ICU readmission, discharge destination). All models were adjusted for a minimum of 18 a priori determined potential confounders.Complete ABCDEF bundle performance was associated with lower likelihood of seven outcomes: hospital death within 7 days (adjusted hazard ratio, 0.32; CI, 0.17–0.62), next-day mechanical ventilation (adjusted odds ratio [AOR], 0.28; CI, 0.22–0.36), coma (AOR, 0.35; CI, 0.22–0.56), delirium (AOR, 0.60; CI, 0.49–0.72), physical restraint use (AOR, 0.37; CI, 0.30–0.46), ICU readmission (AOR, 0.54; CI, 0.37–0.79), and discharge to a facility other than home (AOR, 0.64; CI, 0.51–0.80). There was a consistent dose-response relationship between higher proportional bundle performance and improvements in each of the above-mentioned clinical outcomes (all p < 0.002). Significant pain was more frequently reported as bundle performance proportionally increased (p = 0.0001).ABCDEF bundle performance showed significant and clinically meaningful improvements in outcomes including survival, mechanical ventilation use, coma, delirium, restraint-free care, ICU readmissions, and post-ICU discharge disposition.