Background: In the general intensive care unit (ICU) population the introduction of spontaneous breathing trials and daily sedation interruptions have reduced the duration of mechanical ventilation (MV) and ICU length of stay (LOS). However, patients with ARDS often require high amounts of sedation and analgesia that prolong MV duration and weaning. To our knowledge, these practices have not been investigated specifically in patients with acute respiratory distress syndrome (ARDS). In January 2008 both SBT and DSI were instituted as standard practice at our hospital. In 2013, targeted light sedation also was introduced. We used our ARDS quality assurance data base (spanning 2002-2015) to assess whether patients with ARDS also benefit from these interventions. Methods. The data base was queried for all ARDS survivors and then partitioned into 2 groups: the pre-implementation cohort (June 2002-December 2007) consisting of 401 patients and the post-implementation cohort (January 2009-December 2015) with 634 patients. Ninety-nine ARDS patients from 2008 (the wash-in or transition period) were excluded from the analysis. Data included MV duration, ICU LOS, Lung Injury Score (LIS), Acute Physiology and Chronic Health Evaluation (APACHE II) score, and Simplified Acute Physiology (SAPS II) score, age, Oxygenation Index (OI), and measures of adherance to lung-protective ventilation practices: VT, plateau pressure (Pplat) and driving pressure (plateau pressure-PEEP). Data is reported as mean (± sd); statistical analysis was done using unpaired t-tests. Alpha was set at 0.05. Results: The introduction of SBT and conservative sedation practices was associated with significant reductions in both the duration of MV and ICU LOS. This occurred despite that fact that patients in the post-intervention cohort were significantly older, had significantly higher illness severity scores, more severe lung injury and oxygenation defects at ARDS onset. Conclusion: The introduction of SBT and conservative sedation practices substantially reduced the duration of MV and ICU LOS in patients with ARDS. Arroliga AC, et al. Use of sedatives, opioids and neuromuscular blocking agents in patients with acute lung injury and acute respiratory distress syndrome.