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Background: When early and accurate identification of stroke occurs in the field by Emergency Medical Service (EMS) providers, the chances of reperfusion increases dramatically. Telestroke has made significant strides over the years and hold promise for potential use in the prehospital setting. However, the introduction of such a novel technology within a healthcare system can be complex.Purpose: To describe the use of the combination of clinical simulation and Plan-Do-Study-Act (PDSA) methodology in the design of a mobile prehospital telestroke system.Methods: A multi-stakeholder team with representation from the Departments of Neurology and Emergency Medicine, Office of Telemedicine, Center of Human Simulation and Patient Safety, local EMS agency and a telemedicine developer collaborated to develop a mobile prehospital telestroke system over a 6 month time period. Modifications to telemedicine equipment, teleconferencing software and protocol were implemented based on the results of serial PDSA cycles and clinical simulation testing. We used data collected via direct observation notes, survey results and informal interviews during serial PDSA cycles and clinical simulation to test changes to improve our mobile prehospital telestroke system.Results: (see image of PDSA chart)Conclusion: The combined clinical simulation and PDSA model led to the identification of technical and operational barriers not considered in the original design of the mobile telemedicine platform and placement. Before implementation and financial investment in a mobile prehospital telestroke program, the use of combined clinical simulation and PDSA methodology can improve the quality and optimize the system use. Further PDSA and simulation cycles are needed to improve the design of our mobile system.