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Background: Simulation-based learning has improved medical knowledge, proficiency and performance. The treatment window for acute stroke is limited, making preparedness exceedingly critical. We aimed to assess improvement in performance in first responders to ‘stroke codes’, namely junior Neurology and Emergency Medicine (EM) residents. EM residents were included because EM physicians often make tPA decisions at peripheral and non-academic hospitals.Methods: 14 Neurology and 10 EM residents participated at Upstate Medical University, Syracuse, New York. The simulation consisted of senior Neurology residents playing the roles of stroke patient, CT technician and radiologist, nurse, pharmacist and the stroke fellow on-call. The simulation included the time from patient arrival to acute stroke treatment. Each junior Neurology and EM resident completed this simulation, while the rest of the group observed. Cases included stroke mimics, strokes with large vessel occlusions, dissections, cases ineligible for acute intervention, intracerebral and subarachnoid hemorrhages, basilar thrombosis, wake-up strokes, seizure at onset and dissections. Participants reviewed non-contrast CT head, EKG and CT angiography of the head and neck to make decisions about tPA administration and endovascular interventions. This was followed by a debriefing session by the attending and chief residents. Participants filled a pre-and post-simulation graded questionnaire on medical knowledge and confidence (range 0-25, with higher scores reflecting higher performance).Results: The mean score was 18 (range 14-23) pre-simulation and 22 (range 18-25) post-simulation for Neurology residents and 14 (range 8-24) pre-simulation and 18 (range 10-23) post-simulation for EM residents. For all residents, pre-and post-median score was 17 and 19 (Wilcoxon signed-rank test p<0.0001).Conclusion: Because running an effective stroke code requires coordination and rapid analysis, stroke simulation is an effective way of improving knowledge and confidence among residents and should be integrated into the Neurology and EM residency curriculum.