Introduction: Central venous lines are essential tools in the pediatric ICU (PICU). However, Central-line-associated bloodstream infections (CLABSI) cause significant morbidity and mortality. There are well-described CLABSI risk factors and mitigation strategies. Our smart aim was to decrease the CLABSI rate in the PICU by 30% in 1 year through the development of a risk screening and mitigation tool deployed by a quality improvement (QI) team embedded in daily rounds. Methods: All patients with central venous access were screened daily by the QI team, for the following risk factors: acute behavioral health need, > 72 hours of central access, permanent line, ≥ 25 line accesses per day, impaired skin integrity, immunologic dysfunction, parental nutrition use, extracorporeal support. Any risk factor triggered a CLABSI huddle focused on line necessity, enteral medication conversion, and access reduction. Simultaneous nursing interventions involved prevention education and bundle performance audits. Process measures were followed for the first four months with the primary outcome followed for one year. Results: In the first four months, 19.1% (N=121) patients screened positive for high CLABSI risk, most commonly due to ≥25 line accesses per day (41.7%, n=73). Median total criteria met on initial positive screen was 1 (IQR 1-2). Among positive screens, percutaneous central venous lines (40.5%) and femoral vein location (25.6%) were most prevalent. The most common admitting diagnosis was respiratory failure (22%). Of the 614 positive screens, huddle compliance was 95.9% with ≥ 1 mitigation intervention applied following 20.2% of the huddles. Interventions included line removal (35.7%, n=45), lab modifications (33.3%, n=42), and enteral medication conversion (30.9%, n=39). The annual CLABSI rate decreased from 1.88/1000 line days to 1.18/1000 line days (37.2% decrease). Conclusions: Targeted screening and risk factor mitigation, implemented by dedicated QI team members embedded in rounds, led to a 37.2% reduction in the CLABSI rate in this single center. While this is a promising improvement, sustainability and external validity need to be investigated. Multidisciplinary commitment to reduction of this important complication of critical illness is paramount.