218 patients with unilateral osteoarthritis of the knee were randomized to receive either a single intra-articular injection of non-animal stabilized hyaluronic acid (NASHA) or saline. The purpose of this study was to determine the efficacy and safety of NASHA in patients with mild to moderate osteoarthritis over 6-week follow-up. The results indicated no significant differences in terms of the pain responder rate between groups, defined as a 40% relative reduction and 5pt absolute reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score. However, post-hoc subgroup analysis of patients without clinical effusion at baseline indicated a greater pain responder rate at 6 weeks in the NASHA group compared to the saline group.