Introduction: Emergency Department (ED) resuscitation is a complex, high-stakes procedure where positive outcomes depend upon effective interactions between the healthcare team, the patient, and the environment. To this end, resuscitation teams work in spaces designed to optimize workflows and ensure that necessary treatments and skillsets are available when required. However, systematic failures in this environment cannot always be adequately anticipated, exposing patients to opportunities for harm. As part of a new interprofessional education initiative, this prospective, observational study sought to characterize latent threats to patient safety (LST’s) identified during the delivery of in-situ, simulated resuscitations in two Canadian, tertiary care, academic Emergency Departments. Methods: In-situ simulation sessions were delivered on a monthly basis in the EDs of each hospital campus, during which a variety of simulated resuscitation scenarios were run with distinct teams of ED healthcare professionals. A research assistant was present throughout each session and documented LST’s identified by simulation facilitators and participants during the case and debriefing. Data were entered into a master table and grouped thematically for analysis. Results: After a pilot run-in, 10 in-situ simulation sessions were delivered, involving 27 cases and reaching 180 ED healthcare professionals (25 attending MD, 37 resident MD, 59 RN, 24 RT). 83 latent safety threats were identified through these sessions (mean 3.1 LSTs per case) of which 52 were determined to be “actionable”. Corrective mechanisms have been initiated in 72% of these cases (e.g., new education campaigns and in-servicing, equipment provisioning, equipment checklists). Conclusion: In-situ simulation, beyond its role as a training tool for developing Non-Technical and Crisis Resource Management skills, can be effectively used to identify systematic deficits and knowledge gaps that could expose critically ill patients to harm. Effective quality improvement and continuing education programs are essential to translate these findings into more resilient patient care.