The purpose of this study was to investigate the influence of 8° varus and vaigus shoe modifications on the foot mechanics in overground running. Twenty male subjects performed eight rearfoot running trials in three shoe conditions. Ground reaction forces, tibial accelerations, rearfoot motion, and in-shoe pressure distribution data were collected simultaneously. Between footwear conditions, force and acceleration parameters were found to be significantly different. Compared to the neutral shoe, maximum pronation and pronation velocity were reduced for the varus and increased for the vaigus shoes. Higher lateral rearfoot loads and an increased contribution of the first ray in the forefoot could be evaluated for the vaigus shoe. In contrast, a larger contribution of the medial midfoot and the fifth metatarsal head was observed for the varus shoe. The relative load analysis from the pressure distribution measurements provided additional information about the behavior of the foot in response to major changes in shoe construction.