Background: Timely and effective intervention within the 'golden hour'—the critical first 90 min after the symptom onset—is crucial for initiating life-saving treatment and reducing mortality in acute coronary syndrome (ACS). This highlights the need for nursing students to be proficient in ACS care, emphasizing the importance of preparatory training. This study enhanced traditional simulation methods by integrating a mixed reality (MR) preparation step, offering a more immersive learning experience. We aimed to evaluate the effectiveness of integrating MR preparation into ACS simulation education, focusing on enhancements in knowledge, self-confidence in learning, and self-efficacy in learning. Additionally, we examined performance, practice immersion, and satisfaction to comprehensively evaluate the MR application. Methods: One-group pretest-posttest design was implemented in a convenience sample of thirty-nine senior nursing students from a university in South Korea in August 2022. We developed a simulation program integrating MR preparation into ACS simulation (IMRP-ACSS), which was validated through expert review for content validity. The students participated in the simulation program over six hours across two days, including a 40-minute individual session of MR-based simulation preparation using head-mounted displays (the HoloLens 2). Individual changes in knowledge, self-confidence in learning, and self-efficacy in learning evaluated by the survey were analyzed using paired t-tests. Additionally, group performance assessed using the checklist was analyzed. Immersion and satisfaction were measured with a tool and a 10-point Likert scale, respectively. Results: Individually, participants demonstrated significantly increased knowledge (t = 11.87, p <.001), self-confidence in learning (t = 7.17, p <.001), and self-efficacy in learning (t = 4.70, p <.001) post-education. Group performance yielded a mean score of 56.43/70 ± 7.45. Groups scored higher in electrocardiogram interpretation, patient safety, and heparin administration. Participants reported a practice immersion level of 37.82/50 ± 9.13 and expressed satisfaction with the program, achieving an average score of 8.85/10 ± 1.35. Conclusion: Integrating MR preparation into ACS simulation enhanced nursing students' knowledge, self-confidence in learning, and self-efficacy in ACS care, providing a replicable and immersive learning experience. This method is an effective addition to nursing education, preparing students through comprehensive, technology-enhanced training. [ABSTRACT FROM AUTHOR]