In this article, we describe an Ebola preparedness initiative with implementation across an academic health system. Key stakeholder centers of various disciplines and clinical experts collaborated in the development and design. Subject matter experts in the areas of Centers for Disease Control and Prevention and World Health Organization protocols for personal protective equipment donning and doffing conducted initial train-the-trainer sessions for program instructors. These trainers represented a cross-section of key clinical responders and environmental services. Through a parallel development process, a blended learning curriculum consisting of online modules followed by on-site training sessions was developed and implemented in both the simulation laboratory and the actual clinical care spaces in preparation for a Department of Health inspection. Lessons learned included identification of the need for iterative refinement based on instructor and trainee feedback, the lack of tolerance of practitioners in wearing full-body personal protective equipment for extended periods, and the ability of a large system to mount a rapid response to a potential public health threat through leveraging of expertise of its Simulation Program, Center for Quality, Safety and Innovation as well as a wide variety of clinical departments.