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The purpose of this quality improvement project was to develop an evidence-based protocol designed for pressure injury prevention for neonates and children in a pediatric cardiac care unit located in the Midwestern United States. The ultimate goal of the project was dissemination across all pediatric critical care and acute care inpatient arenas, but the focus of this initial iteration was neonates and children requiring cardiac surgery, extracorporeal support in the form of extracorporeal membranous oxygenation and ventricular assist devices in the cardiac care unit, or cardiac transplantation. A protocol based upon the National Pressure Ulcer Advisory Panel guidelines was developed and implemented in the pediatric cardiac care unit. Pediatric patients were monitored for pressure injury development for 6 months following protocol implementation. During the 40-month preintervention period, 60 hospital-acquired pressure injuries (HAPIs) were observed, 13 of which higher than stage 3. In the 6-month postintervention period, we observed zero HAPI greater than stage 2. We found that development and use of a standardized pressure injury prevention protocol reduced the incidence, prevalence, and severity of HAPIs among patients in our pediatric cardiac care unit.