Simulation in multiple contexts over the course of a 10-week period served as a core learning strategy to orient experienced clinicians before opening a large new urban freestanding emergency department. To ensure technical and procedural skills of all team members, who would provide care without on-site recourse to specialty backup, we designed a comprehensive interprofessional curriculum to verify and regularize a wide range of competencies and best practices for all clinicians. Formulated under the rubric of systems integration, simulation activities aimed to instill a shared culture of patient safety among the entire cohort of 43 experienced emergency physicians, physician assistants, nurses, and patient technicians, most newly hired to the health system, who had never before worked together. Methods throughout the preoperational term included predominantly hands-on skills review, high-fidelity simulation, and simulation with standardized patients. We also used simulation during instruction in disaster preparedness, sexual assault forensics, and community outreach. Our program culminated with 2 days of in-situ simulation deployed in simultaneous and overlapping timeframes to challenge system response capabilities, resilience, and flexibility; this work revealed latent safety threats, lapses in communication, issues of intake procedure and patient flow, and the persistence of inapt or inapplicable mental models in responding to clinical emergencies.