PURPOSE: To compare the effect of unloading knee brace with physical therapy (PT) in Asian patients with osteoarthritis (OA) of the knee. METHOD: This is a non-random, two-group comparative study. Patients with medial compartment knee OA (n = 41) were assigned to either the brace group (n = 20) or PT group (n = 21). Patients in the brace group were fitted with an unloading knee brace for three months and the PT group received a 60-min session of physiotherapy over the affected knee, three times a week, for three months. The primary outcome measures were the pain visual analogue scale (VAS) and the Western Ontario McMaster University Osteoarthritis Index (WOMAC); the second outcome measures were the 36-item Short-Form Health Survey (SF-36) and patient's satisfaction. The patients were evaluated at baseline, and at one month and three months. RESULTS: Group comparison showed no significant difference regarding pain VAS, WOMAC, SF-36, and patient's satisfaction, except stiffness in WOMAC (P = .006) and social functioning in SF-36 (P = .007). Time and group interaction revealed significant differences only in general health (P = .007) and mental health (P = .006) of SF-36. Within-group comparison found that pain VAS and WOMAC decreased significantly at one months and three months in both groups. CONCLUSION: The effect of brace fitting in patients with knee OA was similar to that of physical therapy. A Western-made unloading knee brace is acceptable in some Asian people with knee OA. CLINICAL TRIAL REGISTRATION NUMBER: NCT02712710.