Purpose: This study aimed to develop a mixed reality (MR)-based major trauma nursing simulation training program and evaluate its effectiveness using the Rapid Prototyping Model (RPM). Methods: RPM has 7 steps: analysis, design, prototype, review, development, implementation, and evaluation. To evaluate the effectiveness of the program, a general simulation using a high fidelity simulator was provided to 15 cadets in the control group. A MR-based simulation was provided to 15 cadets in the experimental group. We measured several variables such as simulation design characteristics, student satisfaction, self-confidence, learning flow, clinical performance, and clinical judgment. Results: There was no difference in the homogeneity test between the control and experimental groups. In the experimental group, the improvement of clinical performance and clinical judgment was statistically significant immediately after the intervention. Also, there was statistically significant increase in learning flow after 4 weeks of the intervention. Conclusion: In the process of adapting to new technology and environment, participants had difficulty concentrating on the MR-based simulation program. However, the MR-based simulation has a greater imprinting effect than the general simulation by providing audiovisual patient information. This study suggests to develop a hybrid education program that effectively combines a MR-based major trauma nursing training program with nursing skill practice.