Although medical simulation has not been shown to directly save lives, mounting evidence highlights its ability to decrease clinical protocol violations, increase adherence to guidelines, decrease time to competence, enhance team performance, and increase patient safety. These clinical insights suggest that simulation might offer similar improvements in the design, enrollment, and execution of complex phase 3 clinical research trials. This article provides a theoretical outline of why and how this could be done. Matching the simulation technique with the specific trial uses well-established principles from adult education and process engineering. The goal is to give participants the experiential and emotional involvement that fosters complex thought. Simulation can facilitate "dry runs," role playing, analysis of videos, and "what-if" discussions. Simulated interviews with actors might help with obtaining informed consent and thereby boost enrollment. Simulated phone calls might help with reporting adverse outcomes. Full-body mannequins might be used to confirm that teams can coordinate multiple complex steps. Overall, the goal of simulation in clinical trials is to maximize realism while minimizing logistics and cost. While increased study is needed, this technique has considerable potential to decrease the risk to enrolled patients and to increase the accuracy of study data. Simulation provides an effective tool for immersive, interactive and reflective experiences. Overall, if simulation represents a "revolution in healthcare" then clinicians, patients, and now researchers, all stand to gain.