Background Teaching methods evolve to meet the expanding needs of students, emphasizing not only academic and technical skills but also essential soft skills. Simulation, particularly in virtual reality, plays a pivotal role, fostering technical proficiency and crucial interpersonal skills for healthcare professionals. However, the stress faced by students in simulated scenarios is a critical concern. To enhance the learning experience, our study explores stress levels induced by diverse educational technologies and clinical cases, aiming to provide recommendations for refining simulation training programs for medical students.Methods In longitudinal cohort study at Karaganda Medical University, 57 fifth-year general medicine students underwent a two-week emergency conditions simulation course. Employing 5 simulation techniques, including standardized patients, high-fidelity simulation and various virtual patients, students navigated through 5 challenging clinical scenarios. Learning outcomes were assessed through ongoing tutor assessments and a final OSCE. Stress levels were measured using self-reporting survey and heart rate variability analysis using wearable devices during training sessions. In total, 265 training sessions were ultimately recorded and analyzed using MANOVA and MANCOVA statistical analyses.Results The analysis revealed that educational technologies closely mirroring real situations induce higher psychophysiological stress. Notably, the text-based and screen simulators exhibited lower physiological stress levels than more realistic technologies like standardized patients, high-fidelity and immersive virtual patient simulations. Final OSCE scores were also notably higher for less stressful technologies. The study underscores the nuanced relationship between educational technologies, clinical cases, and learning outcomes, emphasizing the importance of tailored approaches for effective simulation training allowing students to get all required soft skills.Conclusion Restructuring the simulation program involves employing diverse technologies for complex cases and a single technology for simpler ones. Assessing students' psychophysiological states via questionnaires and debriefing is vital for comprehending the impact of educational technologies on effective simulation training.