The influence of teaching leadership on the performance of rescuers remains unknown. The aim of this study was to compare leadership instruction with a general technical instruction in a high-fidelity simulated cardiopulmonary resuscitation scenario. Prospective, randomized, controlled superiority trial. Simulator Center of the University Hospital Basel in Switzerland. Two-hundred thirty-seven volunteer medical students in teams of three. During a baseline visit, the medical students participated in a video-taped simulated witnessed cardiac arrest. Participants were thereafter randomized to receive instructions focusing either on correct positions of arms and shoulders (technical instruction group) or on leadership and communication to enhance team coordination (leadership instruction group). A follow-up simulation was conducted after 4 mos. The primary outcome was the amount of hands-on time, defined as duration of uninterrupted cardiopulmonary resuscitation in the first 180 secs after the onset of the cardiac arrest (hands-on time) [corrected]. Secondary outcomes were time to start cardiopulmonary resuscitation, total leadership utterances, and technical skills. Outcomes were compared based on videotapes coded by two independent researchers. After a balanced performance at baseline, the leadership instruction group demonstrated a longer hands-on time (120 secs; interquartile range, 98-135 vs. 87 secs; interquartile range, 61-108; p < .001), a shorter median time to start cardiopulmonary resuscitation (44 secs; interquartile range, 32-62; vs. 67 secs; interquartile range, 43-79; p = .018), and had more leadership utterances (7; interquartile range, 4-10; vs. 5; interquartile range, 2-8; p = .02) in the follow-up visit. The rate of correct arm and shoulder positions was higher in teams with technical instruction (59%; 19 out of 32; vs. 23%; 7 out of 31; p = .003). Video-assisted leadership and technical instructions after a simulated cardiopulmonary resuscitation scenario showed sustained efficacy after a 4-mo duration. Leadership instructions were superior to technical instructions, with more leadership utterances and better overall cardiopulmonary resuscitation performance.