Purpose of Review <p>Hospital acquired infection (HAI) prevention has been a top priority for healthcare professionals to ensure patient safety. Central line-associated bloodstream infections (CLABSIs) account for over half of all HAIs and are associated with increased morbidity, including prolonged hospital length of stay, mortality, and higher hospital costs. This review briefly discusses the burden of CLABSIs in a pediatric cardiac intensive care unit (CICU) and highlights our approach to current evidence-based practice interventions to aid in CLABSI reduction.</p> Recent Findings <p>Pediatric CICU patients are at an increased CLABSI risk due to their critical status, frequent use of central lines for prolonged periods, limited access availability for placement, and length of hospital stay. Literature has shown that consistent and reliable performance of evidence-based practice interventions can aid in the overall reduction of CLABSIs in various patient populations. Performing these interventions can maintain low CLABSI rates among this patient population. Using rapid Plan-Do-Study-Act cycles beginning in early 2022, we implemented several interventions, including multidisciplinary leadership rounds, a risk identification tool to reduce high CLABSI rates at our institution. In our center, we have demonstrated benefit from interventions described herein.</p> Summary <p>Reducing CLABSI occurrences in pediatric CICU patients can improve patient outcomes, enhance patient safety, and reduce per capita costs to both the patient and institution. Dissemination of reliable evidence-based interventions in this patient population can further be adopted in other institutions to reduce CLABSIs.</p>