253 patients with primary knee osteoarthritis (OA) were randomized to receive a single intra-articular injection of either 6mL Hylan G-F 20 or saline placebo. The purpose of the study was to assess the efficacy of Hylan G-F 20 at reducing pain and improving knee function, as well as to assess the safety of its use. The primary outcome of interest was pain at 26 weeks after injection, as measured by the Western Ontario and McMaster Universities Osteoathritis Index pain subscale (WOMAC A). Secondary outcomes included pain subscores, functional scores (WOMAC C), and a safety analysis. Hylan G-F 20 demonstrated a significantly greater reduction in average pain over the 26 week follow-up from baseline when compared to the placebo group. Patient- and clinical observer global assessment of efficacy also significantly favoured the treatment group. Functional outcome and OMERACT-OARSI responder rate did not significantly differ between groups. Safety analysis demonstrated similar results for the two groups.