The efficacy and safety of SKI306X, a Korean herbal anti-arthritic agent, was compared with that of diclofenac sodium for the treatment of osteoarthritis of the knee. In a randomised, double-blind, active comparator-controlled trial, a total of 249 patients were randomly assigned to receive either 200 mg of SKI306X three times daily or 100 mg of diclofenac sustained release once daily. Clinical efficacy variables (VAS, Lesquesne index and global satisfaction score) and adverse events were monitored at baseline and in the second and fourth weeks of treatment. SKI306X demonstrated efficacy comparable to that of diclofenac, as assessed by the VAS and patients’ and investigators’ global satisfaction score. Both treatments were well tolerated, however, the SKI306X treatment group experienced less heartburn.