Medical misinformation, which contributes to vaccine hesitancy, poses challenges to health professionals. Health professions students, while capable of addressing and advocating for vaccination, may lack the confidence to engage with vaccine-hesitant individuals influenced by medical misinformation. An interprofessional in-person simulation activity (90 minutes) using standardized patients was developed and instituted for students in medicine, nursing, pharmacy, and public health programs. Student volunteers were recruited from classes approximately halfway through their respective degree programs (i.e., second or third year of a 4-year program). Online simulation was used as a method to prepare for in-person simulation. Impact on students was assessed primarily through a postprogram student self-assessment. A total of 220 students participated in the program; 206 (94%) had paired data available to analyze. Following program participation, self-assessed abilities increased from pre to post, from 2.8 out of 5 (good) to 3.9 out of 5 (very good; p < .001). Ninety-eight percent of students felt that their ability to address medical misinformation was somewhat/much better after the activity, compared to before, and that their ability to address vaccine hesitancy was somewhat/much better. The overall program was rated highly, with mean scores for each program evaluation item >4 out of 5 (very good). An interprofessional cohort of students demonstrated improvement in self-assessed skills to participate in a conversation with an individual with hesitancy to receive vaccines and/or beliefs informed by misinformation. Students felt that this program was relevant and important to their professional development.