Merger has served as a major strategy for the leaders of academic medical centers (i.e., teaching hospitals) who are pursuing health system development for their institutions. Applying hindsight to their personal experience, the authors explore common themes in several mergers that have survived the test of time. Although many elements influence merger outcomes, experience suggests several of unique importance. These include effective leadership in the areas of creating trust, managing uncertainty, ensuring medical staff stability, and bridging cultural divides across the organizations. While a quantitative business case should support any merger, the authors’ experiences underscore the importance of successfully assessing and managing organizational and individual dynamics when bringing together major teaching hospitals.