Telemedicine contributes to initiating early intravenous recombinant tissue plasminogen activator (rt-PA) treatment for patients with acute cerebral infarction in areas without a stroke unit. However, the experience and skills of the emergency teams in the spokes to prepare patients and administer rt-PA treatment are ill-defined. Improving these skills could vastly improve management of acute stroke by telemedicine. We developed a medical simulation training model for emergency teams to perform intravenous rt-PA treatment in a telestroke system.From February 2013 to May 2015, 225 learners from 6 emergency teams included in the telestroke system "Virtuall"-in Lorrain (northeastern France)-received a standardized medical simulation training module to perform rt-PA treatment. All learners were assessed with the same pretraining and posttraining test consisting of 52 items. The percentage of right answers was determined for every learner before and after training.Median percentages of right answers were significantly higher in the posttraining test overall (82 ± 10 vs. 59 ± 13% pretraining; P < 0.001), but also in all professional subgroups: physicians (88 ± 8 vs. 67 ± 12%; P < 0.001), paramedical staff (80 ± 9 vs. 54 ± 12%; P < 0.001), nurses (80 ± 8 vs. 54 ± 12%; P < 0.001), and auxiliary nurses (76 ± 17 vs. 37 ± 15%; P = 0.002).We describe for the first time a training model for emergency teams in a telestroke system. We demonstrate significant gain in knowledge for all groups of healthcare professionals. This simulation model could be applied in any medical simulation center and form the basis of a standardized training program of spokes in a telestroke system.