A single intra-articular injection of non-animal stabilized hyaluronic acid (NASHA) was noninferior to methylprednisolone acetate (MPA) for the treatment of pain in knee osteoarthritis (OA) at 12 weeks, according to the results of a prospective, double-blind, multicentre, randomized trial. 442 patients with painful unilateral knee OA were enrolled in the study, and response rates were defined as percentage of patients who achieved ≥40% improvement in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score and an absolute improvement of ≥5 points from baseline. At 12 weeks, 44.6% in the NASHA group and 46.2% in the MPA group showed clinical respones. No serious adverse events were reported. In an open-label extension phase beginning at week 26, treatment with NASHA led to sustained improvements in WOMAC outcomes over a further 26 weeks.