We examined if a subject-specific amount of lateral wedge added to a foot orthosis could alter knee mechanics to potentially reduce the progression of knee osteoarthritis in patients with medial knee osteoarthritis. Twenty individuals with medial knee osteoarthritis (>/=2 Kellgren Lawrence grade) were prescribed a custom laterally wedged foot orthotic device. The prescribed wedge amount was the minimal wedge amount that provided the maximum amount of pain reduction during a lateral step-down test. Following an accommodation period, all subjects returned to the laboratory for a gait analysis. Knee mechanics were collected as the subjects walked at an intentional walking speed. Walking in the laterally wedged orthotic device significantly reduced the peak adduction moment during early stance (p < 0.01) compared to the nonwedged device. Similarly, the wedged orthotic device significantly reduced the knee adduction excursion from heel strike to peak adduction (p < 0.01) compared to the nonwedged device. No differences in the peak adduction moment during propulsion or peak adduction during stance were observed between the orthotic conditions. A subject-specific laterally wedged orthotic device was able to reduce the peak knee adduction moment during early stance, which is thought to be associated with the progression of knee osteoarthritis. Previous studies on this device have reported issues associated with foot discomfort when using wedge amounts >7 degrees; however, no such issues were reported in this study. Therefore, providing a custom laterally wedged orthotic device may potentially increase compliance while still potentially reducing disease progression.