The aim of this study was to compare the efficacy of celecoxib and diclofenac sodium on pain, function and quality of life in patients with knee osteoarthritis (OA). Sixty female patients with knee osteoarthritis diagnosed according to the American College of Rheumatology criteria were randomly assigned to two groups: Thirty five patients in the first group received celecoxib at a dosage of 200 mg/day, and twenty five patients in the second group received 75 mg diclofenac sodium daily. Both medications were applied for a period of 6 weeks. All patients were evaluated in terms of efficacy at baseline, and at 6th week. Pain was evaluated by Western Ontario McMaster Osteoarthritis Index (WOMAC) pain score and visual analogue scale (VAS). Functional capacity was measured by WOMAC physical function index, and quality of life was assessed by the Medical Outcomes Study Short Form-36 Health survey (SF-36). At week 6, both groups showed significant improvement in WOMAC pain, WOMAC physical function and VAS scores (p<0.01), and in physical functioning (p<0.05), physical role (p<0.05), social functioning (p<0.01), mental health (p<0.01), general health (Group 1, p<0.01; Group 2, p<0.05), and pain (Group 1, p<0.01; Group 2, p<0.001) of SF-36. No significant differences in efficacy between the two groups were observed. More patients in the diclofenac group reported adverse events than patients treated with celecoxib (p<0.05). These results suggested that celecoxib is as effective as diclofenac sodium in the treatment of knee OA, with a superior safety profile.