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Purpose: The purpose of this study was to determine the relationship between personality traits, using the Five-Factor Model, and characteristics and motivational factors affecting specialty choice in Korean medical students. Methods: A questionnaire survey of Year 4 medical students (n=110) in July 2015 was administered. We evaluated the personality traits of Extraversion, Agreeableness, Conscientiousness, Neuroticism, and Openness by using the Korean version of Big Five Inventory. Questions about general characteristics, medical specialties most preferred as a career, motivational factors in determining specialty choice were included. Data between five personality traits and general characteristics and motivational factors affecting specialty choice were analyzed using Student t-test, Mann-Whitney test and analysis of variance. Results: Of the 110 eligible medical students, 105 (95.4% response rate) completed the questionnaire. More Agreeableness students preferred clinical medicine to basic medicine (p=0.010) and more Openness students preferred medical departments to others (p=0.031). Personal interest was the significant motivational factors in more Openness students (p=0.003) and Conscientiousness students (p=0.003). Conclusion: Medical students with more Agreeableness were more likely to prefer clinical medicine and those with more Openness preferred medical departments. Personal interest was a significant influential factor determining specialty choice in more Openness and Conscientiousness students. These findings may be helpful to medical educators or career counselors in the specialty choice process.