The most common cause of morbidity and mortality of large mammals in captivity and domesticity is foot disease. Foot pathologies encountered clinically are similar across species, encompassing degenerative, infectious and traumatic disorders. The causes of these pathologies are multifactorial yet the mechanics of foot-ground interaction play a major role- particularly the high forces and pressures during mid-stance loading, which can exacerbate pathology even if not the primary cause. Nevertheless, foot anatomy (and thus mechanics) varies enormously, even among herbivorous quadrupeds. Horses have an extreme foot design with one toe ending in a rigid hoof, which is effective for fast-running but very stiff, and generates large force vibrations during foot impact. Elephants and rhinoceroses represent another extreme: their feet have five and three toes, respectively, bound within a flexible pad of fatty, fibrous tissue (the digital cushion). This digital cushion is heavy and thus costly to swing, but also absorbs and distributes forces and pressures. But how do less extreme foot morphologies, such as those found in domestic cattle and pigs (i.e., even toed ungulate mammals) influence foot mechanics? We developed a novel approach for this study that integrates three-dimensional data from biplanar radiography (XROMM), inverse dynamics, musculoskeletal modelling and finite element analysis to test the hypothesis that the most prevalent pathologies in animal feet occur in anatomical regions that experience the highest stresses during the mid-stance phase of locomotion. We provide our results from the application of this comparative approach to five species of hoofed mammals, ranging from pigs to elephants, to infer how foot form and function evolved, how body size relates to foot mechanics and what the consequences of foot structures and motions are for the risk of pathology.