Purpose: Acute stroke care requires a foundation of clinical knowledge to quickly recognize symptoms and facilitate rapid, safe treatment. Effective care requires a complex network of communication in a stroke response team. Simulation-based training provides a multimodal approach to learning that reinforces clinical knowledge of stroke and affords the opportunity to demonstrate effective communication skills in critical situations. An interprofessional scenario allows all participants to learn about the different roles required for effective care. Methods: Fifty new graduate nurses participated in a pilot model of a traditional didactic session on stroke knowledge, followed by an “escape room” incorporating this knowledge to solve puzzles. The second iteration was expanded to include incoming neurology PGY-2 residents, registered nurses, and pharmacy residents. After the lecture, participants formed teams including equal numbers of all provider roles. The teams were tasked to complete a timed version of the escape room by solving stroke-based puzzles. The escape room was followed by a debrief of communication skills modeled by TeamSTEPPS. Finally, the same teams were exposed to a simulated “stroke code," which included a focused assessment, interpretation of labs and imaging, and management of barriers to treatment with an end goal of collectively managing a suspected stroke. Results: A 5-point scale was used to assess level of comfort with leadership in initial stroke assessment, management, treatment, and communicating concerns. The average increase in numeric level of comfort was 0.9 (range 0.6 - 1.4). The benefit did appear greater for incoming neurology PGY-2 residents (average increase 1.3, range 0.6 - 1.6) compared to registered nurses (average increase 0.45, range 0.25 to 0.75). Conclusions: Use of an escape room during training for incoming neurology PGY-2 residents, registered nurses, and pharmacy residents provided a novel opportunity to facilitate application of clinical knowledge, leadership, teamwork, shared decision-making, and prioritization of patient safety. Providing interactive sessions in between didactic instruction increased participant engagement and level of comfort with roles in a stroke response team.