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Background: Prone position ventilation (PPV) is recommended for patients with severe acute respiratory distress syndrome, but it remains underused. Interprofessional simulation-based training for PPV has not been described., Objectives: To evaluate the impact of a novel interprofessional simulation-based training program on providers' perception of and comfort with PPV and the program's ability to help identify unrecognized safety issues ("latent safety threats") before implementation., Methods: A prospective observational quality improvement study was done in the medical intensive care unit of an academic medical center. Registered nurses, physicians, and respiratory therapists were trained via a didactic session, simulations, and structured debriefings during which latent safety threats were identified. Participants completed anonymous surveys before and after training., Results: A total of 73 providers (37 nurses, 18 physicians, 18 respiratory therapists) underwent training and completed surveys. Before training, only 39% of nurses agreed that PPV would be beneficial to patients with severe acute respiratory distress syndrome, compared with 96% of physicians and 70% of respiratory therapists (P < .001). Less than half of both nurses and physicians felt comfortable taking care of prone patients. After training, perceived benefit increased among all providers. Comfort taking care of proned patients and managing cardiac arrest increased significantly among nurses and physicians. Twenty novel latent safety threats were identified., Conclusion: Interprofessional simulation-based training may improve providers' perception of and comfort with PPV and can help identify latent safety threats before implementation., (Copyright© 2020 American Association of Critical-Care Nurses.)