29 randomized controlled trials, with a total of 4,886 patients were included in this meta-analysis to analyze the safety and efficacy of US-approved viscosupplements in symptomatic knee osteoarthritis (OA) treatment. Results indicated that intra-articular injection of viscosupplements may be safe and effective through 26 weeks, as they resulted in large treatment effects for knee pain and function compared to pre-injection values, and significant treatment effects compared to control saline injection groups. No significant differences were found in safety outcomes or risk adverse events.