368 patients with mild to moderate osteoarthritis of the knee were included in this multicenter randomized controlled trial to investigate the use of a combination injection of cross-linked hyaluronic acid and corticosteroid in comparison to a placebo and an active comparator (hyaluronic acid alone). The primary objective of the study was to determine if the combined injection provided a significant reduction in pain and improved function at 12 and 26 weeks compared to placebo, while also determining if the addition of a corticosteroid accelerates the onset of treatment effects compared to a hyaluronic acid injection alone. The result of this trial indicated that the combination injection met the primary effectiveness endpoint, providing a significantly greater reduction in WOMAC pain compared to placebo through the 12-week follow-up. This significant difference was also observed at the 1, 3, 18, and 26-week follow-ups. Additionally, the combination injection resulted in a significantly faster onset of symptom relief compared to hyaluronic acid at 1 and 3 weeks; these differences were not observed at the week 6-26 follow-ups. Finally, there were no differences in the rate of adverse events between the three groups.