347 patients with knee osteoarthritis were randomized to receive a single injection of either non-animal stabilized hyaluronic acid (NASHA) or saline placebo. The purpose of this study was to compare the effects of NASHA injection on pain reduction, functional improvement, and incidence of adverse events when compared to placebo. Overall data demonstrated that NASHA did not significantly increase treatment response, defined as a 40% relative reduction/5pt absolute reduction on a 20pt Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) pain scale score, throughout 26 week follow-up when compared to patients who received placebo. There was also no significant benefit of the NASHA group regarding reduction in WOMAC pain, stiffness, or physical function scores when compared to placebo.