Pressure ulcers were designated as a priority for quality care initiatives at the University of Pennsylvania Health System. The Penn Medicine Pressure Ulcer Collaborative was developed to address the complex issues of pressure ulcers. The Collaborative used a systematic approach to analyze, plan, and implement a health system–wide pressure ulcer program. As a result, the entire health system had a decrease in hospital-acquired pressure ulcer prevalence rates of 37%. This article describes the Collaborative's innovative approach to quality improvement.