Background: With the recent emphasis on implementation of interprofessional education (IPE), simulation can be a successful and impactful pedagogy to train health profession learners. Simulation allows opportunities to practice decision-making and working in teams in a realistic and safe environment. Participants learn with and about other professions and have the chance to clarify roles within their team. Simulation-enhanced IPE can present challenges for faculty. This article seeks to provide insight into key aspects of interprofessional simulation to maximize its successful implementation. Methods: Our team has identified key lessons learned in how we successfully implemented IPE using simulation. We have collectively overcome challenges and barriers as we have implemented simulation-based IPE at our university. Results: To implement effective simulation-enhanced IPE, teams should consider an overall need assessment, curriculum integration, logistical plans, faculty development, a structured prebrief and debrief plan, and a process for evaluation. Conclusions: Although IPE is an important component of training for future health care providers, simulation can be an effective strategy for implementation of interprofessional activities. However, it is essential to consider key aspects to ensure a quality and consistent experience for learners.