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Purpose: The purpose of this study was to examine the relationship among academic self-efficacy, socially-prescribed perfectionism, and academic burnout in medical school students and to determine whether academic self-efficacy had a mediating role in the relationship between perfectionism and academic burnout. Methods: A total of 244 first-year and second-year premed medical students and first- to fourth-year medical students were enrolled in this study. As study tools, socially-prescribed perfectionism, academic self-efficacy, and academic burnout scales were utilized. For data analysis, correlation analysis, multiple regression analysis, and hierarchical multiple regression analyses were conducted. Results: Academic burnout had correlation with socially-prescribed perfectionism. It had negative correlation with academic self-efficacy. Socially-prescribed perfectionism and academic self-efficacy had 54% explanatory power for academic burnout. When socially-prescribed perfectionism and academic self-efficacy were simultaneously used as input, academic self-efficacy partially mediated the relationship between socially-prescribed perfectionism and academic burnout. Conclusion: Socially-prescribed perfectionism had a negative effect on academic self-efficacy, ultimately triggering academic burnout. This suggests that it is important to have educational and counseling interventions to improve academic self-efficacy by relieving academic burnout of medical school students.