Purpose <p>The study aims to examine how academic stress affects academic achievement among medical graduate students and to explore the moderating role of the Big Five personality traits in the relationship between academic stress and academic achievement.</p> Methods <p>A cross-sectional survey was conducted in December 2024 among 658 participants using an anonymous questionnaire that included three measurement scales (academic stress, academic achievement, and the Big Five personality) and general sociodemographic information. AMOS 26.0 was used to assess the scales' structural validity, and SPSS 26.0 was used to test for common-method bias, provide general descriptive statistics, and conduct correlation analyses. The PROCESS v4.1 macro was used to test for moderated effects.</p> Results <p>Academic stress negatively predicted academic achievement among medical graduate students (β = -0.544, <i>p &lt;</i> 0.001), and the main effects of each factor of academic stress on academic achievement were significant (all <i>p &lt;</i> 0.001). Openness in the Big Five personality played a crucial moderating role in the relationship between academic stress and academic achievement (β = -0.133, F = 144.641, <i>p &lt;</i> 0.05), and it significantly moderated the relationship between each factor of academic stress and academic achievement.</p> Conclusion <p>The higher the academic stress levels, the lower the academic success of medical master's students; however, students with higher open-mindedness personality traits exhibit a weaker negative correlation between stress and academic achievement. This finding suggests that personality traits are a crucial factor closely linked to academic achievement and may play a positive role in stress coping processes, supported by the most extensive study of these relationships to date. It is advised that colleges and universities implement strategies to lower academic stress among medical master's students to improve their academic achievement.</p>