Surgical patients with cancer are at high risk for developing operating room–related hospital-acquired pressure injuries (OR-HAPIs). A nurse-led team at a Magnet-designated comprehensive cancer center was tasked with implementing a quality improvement initiative to reduce the rate of OR-HAPIs. Interventions included the development of a perioperative-specific skin and pressure injury risk assessment, application of prophylactic multilayer foam dressings, electronic health record enhancements, and staff education. The initiative resulted in a 50.5% reduction in OR-HAPIs and an estimated cost avoidance of $80,210 per year.