Background: Innovation has been a central focus of the Department of Surgery at the Brigham and Women's Hospital since its very inception. Here we review examples of innovations originating in this Department and analyze factors that have been critical to successful innovation. Finally, we discuss challenges to sustainability of innovation in this Department. Methods: Narrative review of the literature, interviews, and personal observations. Results: Examples of innovations reviewed here were each dependent on three critical elements: 1) multidisciplinary collaboration among surgical innovators and individuals outside of surgery who offered complementary skills and expertise, 2) a rich institutional environment that sustained a diverse complement of innovators working in close proximity, and 3) Department Chairmen who facilitated the work of innovators and promoted their contributions, rather than seeking personal prestige or financial gain. Contemporary challenges to sustainability of innovation include the prevailing emphasis on clinical efficiency and on cost containment. Conclusion: We have identified factors critical to successful innovation in a Department of Surgery. The relevance of these factors is unlikely to be diminished, even in the changing landscape of modern medicine. © Copyright 2017, Mary Ann Liebert, Inc. 2017.