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The effects of lateral wedge insole with and without sub-talar strap on pain, arthritic symptoms, functional performance, sports and recreational activities, and knee related quality of life in patients with medial compartment knee osteoarthritis were compared. Community-dwelling men and women aged over 40 years with medial compartment knee osteoarthritis, grades I or II based on Kellgrene and Lawrence grading system were participated in this study. They were randomly allocated in two different groups; lateral wedge insole with and without sub-talar strap. Both groups were required to wear the insoles at home for the duration of four weeks, approximately 5 to 10 hours per day. Participants were asked to complete the Farsi version of Knee injury and Osteoarthritis Outcome Score [KOOS] questionnaire at baseline and at follow-up. The reliability of KOOS for measuring short term and long term symptoms and function in Iranian patients with knee injuries and osteoarthritis has been reported previously. The changes in KOOS subscales were significantly different in both groups over time. Contrary to our hypothesis, the interaction effect was significant between the two groups following our intervention in terms of symptoms, daily living functions, sports and recreational activities, and knee related quality of life, unless pain score. The result of this study suggests that both of the insoles improved pain, symptoms, function in daily living, sports and recreation activities and knee related quality of life in patients with mild medial compartment knee osteoarthritis. However, use of sub-talar strap with lateral wedge insole would be the better prescription for insoles in these patients.