255 patients, over the age of 40, with a diagnosis of knee osteoarthritis were randomized to receive either appropriate care alone or 3 intra-articular injections of hylan G-F 20 at 1-week intervals in addition to appropriate care. The purpose of this randomized controlled trial was to determine the clinical effectiveness of hylan G-F 20 injections in terms of disease-specific outcomes and health-related quality of life. The results displayed that hylan G-F 20 and appropriate care lead to significant and clinically important improvements in WOMAC pain at 12 months, as well as significant improvements in health-related quality of life, patient global assessments of treatment effectiveness, and safety outcomes when compared to appropriate care alone.