Since the early 2000s our research groups in Belgium and Australia have been intrigued by the interaction between endurance exercise and the heart. Despite the widely established benefits of regular exercise, we put forward the concept that too much exercise may cause damage to the heart in a small subset of athletes. There are multiple studies that have been performed in athletes but almost all of these have assessed athlete’s health at a single point in time. Thus, it is not possible to determine whether observations (positive or negative) are due to exercise or pre-existing health status. The aim of our collaborative research projects (Pro@Heart, Master@Heart and ProAFHeart) is to rigorously assess the long-term health effects of high-level exercise. We aim to create the largest prospective study in the world by collaborating with international leaders in sports cardiology, radiology, exercise science, genetics and population health. It is to be expected that the number of international collaborators will increase over time so that the study can provide a description of athletes from multiple nations and various sporting pursuits.