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Background and Objectives: Few studies have demonstrated improvement in adherence to Pediatric Advanced Life Support guidelines for severe sepsis and septic shock. We sought to improve adherence to national guidelines for children with septic shock in a pediatric emergency department with poor guideline adherence., Methods: Prospective cohort study of children presenting to a tertiary care pediatric emergency department with septic shock. Quality improvement (QI) interventions, including repeated plan-do-study-act cycles, were used to improve adherence to a 5-component sepsis bundle, including timely (1) recognition of septic shock, (2) vascular access, (3) administration of intravenous (IV) fluid, (4) antibiotics, and (5) vasoactive agents. The intervention focused on IV fluid delivery as a key driver impacting bundle adherence, and adherence was measured using statistical process control methodology., Results: Two-hundred forty-two patients were included: 126 subjects before the intervention (November 2009 to March 2011), and 116 patients during the QI intervention (October 2011 to May 2013). We achieved 100% adherence for all metrics, including (1) administration of 60 mL/kg IV fluid within 60 minutes (increased from baseline adherence rate of 37%), (2) administration of vasoactive agents within 60 minutes (baseline rate of 35%), and (3) 5-component bundle adherence (baseline rate of 19%). Improvement was sustained over 9 months. The number of septic shock cases between each death from this condition increased after implementation of the QI intervention., Conclusions: Using QI methodology, we have demonstrated improved adherence to national guidelines for severe sepsis and septic shock., (Copyright © 2014 by the American Academy of Pediatrics.)