The results of conservative treatment of knee osteoarthritis (OA) are generally evaluated in epidemiological studies with clinical outcome measures as primary outcomes. Biomechanical evaluation of orthoses shows that there are potentially beneficial biomechanical changes to joint loading; however, evaluation in relation to clinical outcome measures in longitudinal studies is needed. We asked (1) is there an immediate effect on gait in patients using a laterally wedged insole or valgus knee brace; (2) is there a late (6 weeks) effect; and (3) is there a difference between subgroups within each group with respect to patient compliance, body mass index, and OA status? This was a secondary analysis of data from a previous randomized controlled trial of patients with early medial knee OA. A total of 91 patients were enrolled in that trial, and 73 (80%) completed it after 6 months. Of the enrolled patients, 80 (88%) met prespecified inclusion criteria for analysis in the present study. The patients were randomized to an insole or brace. Gait was analyzed with and without wearing the orthosis (insole or brace) at baseline and after 6 weeks. Measurements were taken of the knee adduction moment, ground reaction force, moment arm, walking speed, and toe-out angle. Data were analyzed with regression analyses based on an intention-to-treat principle. A mean reduction of 4% (+/- A 10) (95% confidence interval [CI], -0.147 to -0.03, p = 0.003) of the peak knee adduction moment and 4% (+/- A 13) (95% CI, -0.009 to -0.001, p = 0.01) of the moment arm at baseline was observed in the insole group when walking with an insole was compared with walking without an insole. A mean reduction of 1% (+/- A 10) (95% CI, -0.002 to -0.001, p = 0.001) of the peak knee adduction moment and no reduction of the moment arm were measured after 6 weeks. No reduction of knee adduction moment, moment arm, or ground reaction force was seen in the brace group at baseline and after 6 weeks. Subgroup analysis showed no differences in biomechanical effect for obesity, stage of OA, and whether patients showed a clinical response to the treatment. Laterally wedged insoles unload the medial compartment only at baseline in patients with varus alignment and by an amount that might not be clinically important. No biomechanical alteration was seen after 6 weeks of wearing the insole. Valgus brace therapy did not result in any biomechanical alteration. Taken together, this study does not show a clinically relevant biomechanical effect of insole and brace therapy in patients with varus medial knee OA. Level I, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.