Introduction: Simulation of the clinical setting incorporates an educational approach connecting a learner to a particular environment of learning. Undergraduate students in the health sector experience anxiety during simulation that influences their performance which ultimately affects their learning outcome. This study attempts to correlate the impact of stressors on learning outcome of high-fidelity patient simulation (HFPS) in undergraduate medical education. Objective: This research is to analyze the impact of stressors and its relevance on the learning outcome of HFPS as a teaching-learning tool for the management of emergency surgical conditions including trauma. Materials and Methods: This study is a Quasi-experimental time series design. A total number of 347 final-year undergraduate (MBBS) students of Melaka-Manipal Medical College, Malaysia. They were grouped and assessed individually by pre-test and post-tests on their knowledge, performance and associated stressor scores. The one-way repeated measure of Analysis of Variance (ANOVA) was used to determine the statistically significant differences in total score at pre-test simulation and post-test-simulation sessions. Friedman test was used for assessment of individual components of stressors. Pre-test and post-tests scores were compared to note progress in confidence and stress reduction. P value <0.001 was considered statistically significant. Results: ANOVA with Bonferroni post hoc analysis showed a statistically significant (p <0.001) difference in stressor score over time. The drop-in stress was significant initially but flattened out later. Conclusion: Stress significantly decreased as the students were exposed to more sessions of HFPS which ultimately translated into better learning outcome.