Many medical schools incorporate assessments of personal characteristics, including personality traits, in their selection process. However, little is known about whether changes in personality traits during medical training affect the predictive validity of personality assessments. The present study addressed this issue by examining the stability of personality traits and their predictive validity over a 6-year medical training course. Participants were two cohorts of Swiss medical students (N = 272, 72% of students admitted to Year 2) from whom we collected demographic data, Swiss medical studies aptitude test (EMS) scores, Big Five personality traits scores measured at three times and scores on the multiple-choice and objective structured clinical examination parts of the final medical examination. Our findings indicated that personality traits had medium-to-high rank-order stability ( r > .60 over 3 years and r > .50 over 6 years). Mean-level changes were moderate for agreeableness ( d = + 0.72) and small for neuroticism and conscientiousness ( d = -0.29, d = -0.25, respectively). Individual reliable change indices ranged from 4.5% for openness to 23.8% for neuroticism. The predictive validity was similar to that of the first three years of follow-up. To the best of our knowledge, this is the first study to investigate changes in personality across undergraduate curriculum. Medical students’ personality traits were mostly stable across medical school and retain their predictive validity. Consequently, this study supports the use of tools measuring constructs underlying personality traits in selection. In addition, this study confirms that examination formats could favor students with certain personality traits.