Objective: Nonsteroidal anti-inflammatory drugs (NSAID) are among the most widely prescribed agents in osteoarthritis patients, and may lead to important side-effects which increase the risk of hospitalization and death. Transdermal administration of NSAIDs can provide relief of pain locally with relatively less side effects. This study was aimed to evaluate the efficacy of a single administration of 40 mg transdermal flurbiprofen on pain and on strength of quadriceps and hamstring muscles in patients with knee osteoarthritis. Material and Methods: This study is a double blind, placebo-controlled cross-over preliminary study. Transdermal flurbiprofen and placebo patches were administered to the 24 patients with knee osteoarthritis. Knee pain was evaluated using a visual analog scale (VAS) and the strength of quadriceps and hamstring muscles using an isokinetic dynamometer. Results: Mean VAS scores reduced from 5.3 +/- 1.7 to 4.7 +/- 1.6 (p= 0.88) after placebo administration, and from 5.4 +/- 1.9 to 3.9 +/- 1.7 (p= 0.04) following flurbiprofen administration. Peak torque and total work values of flexor and extensor muscles of knee did not differ statistically after flurbiprofen or placebo administrations. Conclusion: Pain significantly reduced after single dose of transdermal flurbiprofen patch. However, no significant difference in isokinetic assessment parameters was observed in the present study. To assess the effects of transdermal flurbiprofen and its efficacy on knee pain and function, further controlled studies in larger groups of patients with different doses of flurbiprofen are recommended.