High-fidelity simulation is increasingly popular in interprofessional education (IPE). This study aimed to determine the effectiveness of high-fidelity simulation in teaching IPE content to prelicensure trainees. A quasi-experimental study took place at a simulation center in Southern California. It assessed medical and nursing students' teamwork skills and attitudes toward IPE before and after high-fidelity simulation. Multivariate analysis of variance results revealed a decline in positive attitudes toward IPE postintervention in both medical and nursing students. No changes in teamwork skills and no differences between nursing and medical trainees were found. The implications of the study's findings are discussed.