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Objectives: Efforts to mitigate unexpected problems during transition of an active emergency department (ED) to a new physical plant are imperative to ensure effective health care delivery and patient safety. The authors used advanced medical simulation (SIM) to evaluate the capacity of a new ED for emergent resuscitative processes and assist facility orientation before opening day. Methods: Operational readiness testing and orientation to the new ED of a large academic center were arranged through a Transportable Enhanced Simulation Technologies for Pre-Implementation Limited Operations Testing (TESTPILOT) project. Using a portable life-sized computerized manikin, the project required participants to perform assorted patient care interventions on-site. Cardiac arrest, multitrauma, uroseptic shock, and pediatric toxicology scenarios elicited the dynamics of real-life ED activities. Debriefings and surveys assessed participants' perceptions of the new facility's clinical readiness and identified areas needing administrative attention. Subjective utility of SIM orientation was compared with that of standard facility orientation. Results: Fourteen ED clinicians and five SIM facilitators participated over two sessions. The new facility received mean (± SD) and median five-point Likert scale scores of 4.4 (± 0.8) and 5 for ability of clinical staff to perform resuscitations. The respective scores for ability of simulated scenarios to prepare staff for new ED function were 4.6 (± 0.5) and 5, compared with 4.2 (± 1.0) and 4 for non-SIM orientation (p = 0.22; not significant). Problems with equipment location, inadequate procedural surfaces, and insufficient orientation were discovered and rapidly corrected. Conclusions: Transportable SIM was used to evaluate the clinical functions of a new ED. Significant operational issues identified by participants were corrected before opening of the facility. Limited comparison did not reveal SIM enhancement of orientation.