Purpose: Physical therapists (PTs) perform early mobilization in the intensive care unit (ICU), but specialized knowledge, skills, and behaviors for ICU clinical practice pose unique challenges. High-fidelity human simulation (HFHS) training prepares medical professionals for ICU practice, but evidence on HFHS training for PTs is limited. The purpose was to develop and evaluate an HFHS-based training program focused on improving PTs' self-efficacy for ICU clinical practice. Methods: Six PTs participated in 3 immersive HFHS experiences, each including a simulation and group debriefing. All participants completed self-efficacy surveys pre- and posttraining. A focus group was conducted to gather participant perspectives on the learning experience. Results: Significant improvements in 3 self-efficacy categories occurred: performing a chart review, understanding precautions/medications, and implementing early mobilization. Qualitative analysis of the focus group revealed 4 themes: simulation facilitates positive reinforcement and confidence building; collaborative learning in a safe environment promotes skill acquisition, teamwork in training improves clinical collaboration; and simulation provides effective orientation to complex line management. The small sample size and unknown psychometric properties of the self-efficacy scale limit these results. Conclusions: The HFHS program facilitated PTs' teamwork, collaboration, and self-efficacy for ICU clinical practice. Further investigation is recommended to evaluate the efficacy of HFHS as a training tool to enhance PT practice in the ICU.