Cycling is commonly prescribed for individuals with knee osteoarthritis (OA) but very little biomechanical research exists on the topic. Individuals with OA may be at greater risk of OA progression or other knee injuries because of their altered knee kinematics. This study investigated the effects of lateral wedges on knee joint biomechanics and pain in patients with medial compartment knee OA during stationary cycling. Thirteen participants with OA and 11 paired healthy participants volunteered for this study. A motion analysis system and a customized instrumented pedal were used to collect 5 pedal cycles of kinematics and kinetics, respectively, during 2 minutes of cycling in 1 neutral and 2 lateral wedge (5° and 10°) conditions. Participants pedaled at 60 RPM and an 80 W workrate and rated their knee pain on a visual analog scale during each minute of each condition. There was a 22% decrease in the internal knee abduction moment with the 10° wedge. However, this finding was not accompanied by a decrease in knee adduction angle or subjective pain. Additionally, there was an increase in vertical and horizontal pedal reaction force which may negate the advantages of the decreased internal knee abduction moment. For people with medial knee OA, cycling with 10° lateral wedges may not be sufficient to slow the progression of OA beyond the neutral riding condition.