In medical education, consistent and repetitive practice are crucial for mastering highly technical skills and clinical diagnosis. Hands-on experience and simulations play a vital role in developing these competencies. Objective structured clinical examinations (OSCEs) assess these skills, though they can induce stress, which may impact clinical performance both positively and negatively. This study, registered with the Australian New Zealand Clinical Trials Registry (ACTRN12623001214628), assessed psychophysiological responses and clinical decision-making skills of 26 undergraduate paramedicine students completing two high-acuity simulated OSCE assessments. We found that when participants completed their second scenario seven days after their initial attempt, a significant decrease in cortisol concentration (p = 0.016), heart rate variability (p = 0.021), skin temperature (p = 0.045) and perspiration levels (p textless .001) were recorded. We also observed earlier neural activation suggesting participants were forming crucial clinical decisions and prioritising tasks more quickly in the second scenario. Importantly, clinical performance also improved significantly (p textless .001). Our findings support the inclusion of repeated high-acuity simulation practice in OSCE assessments to help students develop confidence, improve decision-making under stress, and ultimately enhance clinical outcomes.