BACKGROUND: Knee osteoarthritis (OA) is an incurable joint disorder, representing a major public health issue. Among options for symptom control, viscosupplementation with hyaluronic acid (HA) had established usefulness in pain and function improvement of the knee. However, it is not clear which form of HA yields better results.MATERIAL AND METHODS: We compared two HA preparations with high (HMW) or low molecular weight (LMW) in terms of pain control and function improvement using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the visual analog scale (VAS) score in patients with knee OA. During 2013, 80 patients were enrolled in this prospective, double-blind, randomized study. Each patient received a weekly injection of either preparation with a total of five injections for the LMW group and three for the HMW group. They were evaluated at baseline, five weeks, three months and one year after treatment.RESULTS: In both groups, HA treatment resulted in significant improvement in pain and function that begun immediately after treatment and lasted for one year. However when compared with each other, HMW and LMW groups were comparable in mean WOMAC, and VAS score at each time point. Neither preparation can interrupt disease progression as radiological findings remained constant during follow-up.CONCLUSIONS: Intra-articular injections using HMW or LMW HA can improve stiffness, joint function and pain in patients suffering from knee OA. However, no clear benefit seems to exist between the two preparations and neither can slow disease progression. Hippokratia 2016, 20(1): 26-31.