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A large body of research using simulation in healthcare has focused on simulation itself as an object of research. However, simulation can also be used in research on human or system performance. It can be used to investigate the effects of performance shaping factors that would otherwise be difficult to study in the actual clinical setting due to practical constraints or ethical concerns. In this monograph, we illustrate various ways in which simulation has been used to study performance shaping factors. We also discuss possible directions for future research as well as methodological considerations for researchers engaging in this approach to study performance shaping factors.