Academic medical centers (AMCs) could advance the science of health care delivery, improve patient safety and quality improvement, and enhance value, but many centers have fragmented efforts with little accountability. Johns Hopkins Medicine, the AMC under which the Johns Hopkins University School of Medicine and the Johns Hopkins Health System are organized, experienced similar challenges, with operational patient safety and quality leadership separate from safety and quality-related research efforts. To unite efforts and establish accountability, the Armstrong Institute for Patient Safety and Quality was created in 2011.The authors describe the development, purpose, governance, function, and challenges of the institute to help other AMCs replicate it and accelerate safety and quality improvement. The purpose is to partner with patients, their loved ones, and all interested parties to end preventable harm, continuously improve patient outcomes and experience, and eliminate waste in health care. A governance structure was created, with care mapped into seven categories, to oversee the quality and safety of all patients treated at a Johns Hopkins Medicine entity. The governance has a Patient Safety and Quality Board Committee that sets strategic goals, and the institute communicates these goals throughout the health system and supports personnel in meeting these goals. The institute is organized into 13 functional councils reflecting their behaviors and purpose. The institute works daily to build the capacity of clinicians trained in safety and quality through established programs, advance improvement science, and implement and evaluate interventions to improve the quality of care and safety of patients.