This study assessed the biomechanic effects of wearing a lateral wedge on the subtalar joint moment during gait in athletes with and without an unstable lateral ankle. A crossover design was applied whereby 50 collegiate males walked with two different wedges: a 0 degrees control wedge and a 6 degrees lateral wedge. We investigated frontal plane angles and moments at the subtalar joint and the knee joint, as well as ground reaction forces and center of pressure excursion. Moments were derived using a three-dimensional inverse dynamics model of the lower extremity. The 6 degrees lateral wedge significantly increased the subtalar joint valgus moment (P < 0.001) and reduced the knee joint varus moment (P < 0.001) when compared with no wedge. The differences between wedge conditions were associated with a laterally shifted location of the center of pressure during stance phase. However, there were diverse, sometimes reversed effects with the wedge among the athletes with an unstable lateral ankle. These results indicate that biomechanical indications and limitations of lateral wedges in unstable lateral ankles should be analyzed in more detail, possibly leading to new guidelines for the use of such foot orthoses.