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Background: Medial knee osteoarthritis can contribute to pain and stiffness, interfere with balance and limit functional activities of daily living. Unloader knee orthosis or lateral wedged insoles are current conservative approaches used to treat these conditions. The aim of this study was to identify and compare the effects of them on the balance parameters. Methods: 66 subjects with mild to moderate medial knee osteoarthritis were randomly assigned to wear unloader knee brace or full-length 6° lateral wedge insole. Primary outcome balance parameters were stability %, path length and average velocity of center of pressure and mobility score which were investigated by HUMAC® Balance and Tilt system. Secondary outcome measures were knee function score using Knee Injury and Osteoarthritis Outcome Score scale. Assessment was performed at baseline and six months post orthotic intervention period. Findings: Both orthoses improved all parameters compared to the baseline condition (p < 0.05). Unloader knee orthosis showed a significant improvement in all balance parameters compared to lateral wedged insoles (p < 0.001) except mobility scores (p=0.527). Except activities of daily living (p=0.752) and sports and recreational activities (p=0.437), unloader knee orthosis had a greater effect on the pain (p=0.002) and symptoms (p < 0.001) sub scales than lateral wedged insoles. However, quality of life sub-scale scores for insoles were more effective than the knee orthosis. Interpretation: Unloader knee orthosis improved balance and knee function scores more than lateral wedged insole, though both orthoses produced significantly improved results compared to baseline assessment. [ABSTRACT FROM AUTHOR]