The goal of this study was to examine the influence of changes in foot positioning at touch-down on ankle sprain occurrence. Muscle model driven computer simulations of 10 subjects performing the landing phase of a side-shuffle movement were performed. The relative subtalar joint and talocural joint angles at touchdown were varied, and each subject-specific simulation was exposed to a set of perturbed floor conditions. The touchdown subtalar joint angle was not found to have a considerable influence on sprain occurrence, while increased touchdown plantar flexion caused increased ankle sprain occurrences. Increased touchdown plantar flexion may be the mechanism which causes ankles with a history of ankle sprains to have an increased susceptibility to subsequent sprains. This finding may also reveal a mechanism by which taping of a sprained ankle or the application of an ankle brace leads to decreased ankle sprain susceptibility.