The purpose of this study was to determine prospectively gait related risk factors for exercise-related lower leg pain (ERLLP) in 400 physical education students. Static lower leg alignment was determined, and 3D gait kinematics combined with plantar pressure profiles were collected. After this evaluation, all sports injuries were registered by the same sports physician during the duration of the study. Forty six subjects developed ERLLP and 29 of them developed bilateral symptoms thus giving 75 symptomatic lower legs. Bilateral lower legs of 167 subjects who developed no injuries in the lower extremities served as controls. Cox regression analysis revealed that subjects who developed ERLLP had an altered running pattern before the injury compared to the controls and included (1) a significantly more central heel-strike, (2) a significantly increased pronation, accompanied with more pressure underneath the medial side of the foot, and (3) a significantly more lateral roll-off. These findings suggest that altered biomechanics play a role in the genesis of ERLLP and thus should be considered in prevention and rehabilitation.