Introduction Physician interpersonal competence is crucial for patient care. How interpersonal competence develops during undergraduate medical education is thus a key issue. Literature on the topic consists predominantly of studies on empathy showing a trend of decline over the course of medical school. However, most existing studies have focused on narrow measures of empathy. The first aim of this project is to study medical students' interpersonal competence with a comprehensive framework of empathy that includes self-reported cognitive and affective empathy, performance-based assessments of emotion recognition accuracy, and a behavioural dimension of empathy. The second aim of the present project is to investigate the evolution of mental health during medical school and its putative link to the studied components of interpersonal competence. Indeed, studies documented a high prevalence of mental health issues among medical students that could potentially impact their interpersonal competence. Finally, this project will enable to test the impact of mental health and interpersonal competence on clinical skills as evaluated by experts and simulated patients. Methods and analysis This project consists of an observational longitudinal study with an open cohort design. Each year during the four consecutive years of the project, every medical student (curriculum years 1-6) of the University of Lausanne in Switzerland will be asked to complete an online questionnaire including several interpersonal competence and mental health measures. Clinical skills assessments from examinations and training courses with simulated patients will also be included. Linear mixed models will be used to explore the longitudinal evolutions of the studied components of interpersonal competence and mental health as well as their reciprocal relationship and their link to clinical skills. Ethics and dissemination The project has received ethical approval from the competent authorities. Findings will be disseminated through internal, regional, national and international conferences, news and peer-reviewed journals.