This is the first study to provide a holistic examination of cardiologists’ well-being, investigating positive and negative dimensions, and its determinants. We conducted a national, multicenter, self-administered web-based questionnaire. We used frequencies to depict scores on three well-being indicators (professional fulfillment, work exhaustion and interpersonal disengagement) and performed three multiple regression analyses to elucidate their determinants. Cardiologists’ mean scores (scale 1 to 5) were 3.85 (SD = 0.62) for professional fulfillment, 2.25 (SD = 0.97) for work exhaustion and 2.04 (SD = 0.80) for interpersonal disengagement. Workload, work-home interference and team atmosphere predicted the negative dimensions of well-being. Autonomy predicted cardiologists’ professional fulfillment. Physician-patient interactions, person-job fit and individual resilience affected both dimensions. Dutch cardiologists score relatively high on professional fulfillment and average on work exhaustion and interpersonal disengagement. In order to foster cardiologists’ well-being it is critical to increase energy providing work- and individual aspects.