This meta-analysis included 89 studies (177 reports) that compared viscosupplementation with a sham injection or no control intervention in adult patients with knee osteoarthritis (OA). 12 667 patients in total were identified from these 89 studies. The results from the analysis demonstrated that viscosupplementation provided a reduction in pain compared to the control intervention. Statistical significance was also demonstrated when the analysis was restricted to large trials with blinded outcome assessment, although the effect size was reduced compared to the primary analysis. Additionally, a sub-group analysis illustrated a greater effect size with very-high and high molecular weight compared to low molecular weight hyaluronate. A safety analysis indicated viscosupplementation tended to be associated with an increased risk of adverse events and flare-ups. However, further evaluation is required to determine if the causal mechanisms of the adverse events are related to viscosupplementation.