Academic medical centers (AMCs) face unique challenges in translating their innovation in safety and quality research into clinical performance. This study examined discharge data from 79 AMCs to generate a scoring method for measures of safety, mortality, clinical effectiveness, and equity of care. After identifying three top performers and three average performers, a group of surveyors visited each site without knowledge of their score and made an objective assessment of the factors associated with their performance. The authors highlight the importance of a shared sense of purpose, a hands-on leadership style, accountability systems for quality and safety, a focus on results, and a culture of collaboration as key predictors of top performers. Similar to a past study that evaluated safety culture in AMCs, the authors emphasize that the actions of senior executives and department chairs do impact care at the bedside.