Objectives: This study investigates: (1) which personality traits are typical of medical students as compared to other students, and (2) which personality traits predict medical student performance in pre-clinical years. Design: This paper reports a cross-sectional inventory study of students in nine academic majors and a prospective longitudinal study of one cohort of medical students assessed by inventory during their first pre-clinical year and by university examination at the end of each pre-clinical year. Subjects and methods: In 1997, a combined total of 785 students entered medical studies courses in five Flemish universities. Of these, 631 (80.4%) completed the NEO-PI-R (i.e. a measure of the Five-Factor Model of Personality). This was also completed by 914 Year 1 students of seven other academic majors at Ghent University. Year end scores for medical students were obtained for 607 students in Year 1, for 413 in Year 2, and for 341 in Year 3. Results: Medical studies falls into the group of majors where students score highest on extraversion and agreeableness. Conscientiousness (i.e. self-achievement and self-discipline) significantly predicts final scores in each pre-clinical year. Medical students who score low on conscientiousness and high on gregariousness and excitement-seeking are significantly less likely to sit examinations successfully. Conclusions: The higher scores for extraversion and agreeableness, two dimensions defining the interpersonal dynamic, may be beneficial for doctors' collaboration and communication skills in future professional practice. Because conscientiousness affects examination results and can be reliably assessed at the start of a medical study career, personality assessment may be a useful tool in student counselling and guidance.