Tehran University of Medical Sciences Acta Medica Iranica 0044-6025 65 5 2026 07 06 286 293 Reza valizadeh Department of Medicine, Ilam University of Medical Sciences, Ilam, Iran. Maryam Zinivand School of Medicine, Ilam University of Medical Sciences, Ilam, Iran. Aliashraf Mozafari Department of Epidemiology, School of Health, Psychosocial Injuries Research Center, Ilam University of Medical Sciences, Ilam, Iran. Sehat Aibod Department of Psychology, Psychosocial Injuries Research Center, Ilam University of Medical Sciences, Ilam, Iran. Sajad Sohrabnejad Department of Clinical Psychology, School of Medicine, Ilam University of Medical Sciences, Ilam, Iran 2025 10 18 2026 05 31 Medical students face multiple academic and clinical stressors that can compromise their psychological well-being. Identifying protective psychological factors is crucial for developing effective mental health promotion and prevention strategies in university settings. This study examined the relationships between personality traits, self-compassion, and psychological well-being among medical students, focusing on their potential preventive roles. A cross-sectional correlational study was conducted with 162 medical students. Participants completed the NEO Five-Factor Inventory (NEO-FFI), the Self-Compassion Scale (SCS), and the Psychological Well-Being Scale (PWB). Data were analyzed using descriptive statistics, Pearson’s correlations, and multiple regression analyses (α<0.05). Mean scores were Neuroticism 22.96±4.87, Extraversion 26.15±5.02, Openness 27.78±4.65, Agreeableness 29.89±5.41, Conscientiousness 30.23±5.12, Self-Compassion 41.13±5.94, and Psychological Well-Being 67.52±8.91. Psychological well-being correlated positively with Openness to Experience (r=0.21, P=0.02) and Conscientiousness (r=0.25, P=0.01). Gender differences were significant for Extraversion, Openness, and the “Common Humanity” dimension of self-compassion (P<0.05). Regression analysis indicated that personality traits significantly predicted psychological well-being (β=0.19, P=0.04), whereas self-compassion was not a direct predictor (β=0.03, P=0.93). Conscientiousness and Openness to Experience play pivotal roles in medical students’ psychological well-being. Notably, this study found no direct predictive relationship between self-compassion and well-being. Rather than a lack of relevance, this finding suggests that in the rigorous context of medical education, self-compassion may function through indirect mechanisms or act as a moderating factor. These findings underscore the importance of interventions that enhance adaptive personality traits, while highlighting the need for a more nuanced understanding of how self-compassion contributes to resilience and sustainable mental health in high-pressure academic settings. Conscientiousness and Openness to Experience play pivotal roles in medical students’ psychological well-being. Notably, this study found no direct predictive relationship between self-compassion and well-being. Rather than a lack of relevance, this finding suggests that in the rigorous context of medical education, self-compassion may function through indirect mechanisms or act as a moderating factor. These findings underscore the importance of interventions that enhance adaptive personality traits, while highlighting the need for a more nuanced understanding of how self-compassion contributes to resilience and sustainable mental health in high-pressure academic settings. https://acta.tums.ac.ir/index.php/acta/article/view/11848 https://acta.tums.ac.ir/index.php/acta/article/download/11848/6053