BACKGROUND: Knee osteoarthritis (KOA) is a common joint disorder, and intra-articular injections of hyaluronic acid (HA) or platelet-rich plasma (PRP) are frequently employed therapeutic interventions. However, there remains controversy regarding their efficacy. This systematic review aims to compare the effectiveness and safety of HA and PRP through a meta-analysis, with the objective of identifying the optimal treatment protocol for KOA and enhancing its management. METHODS: Randomized controlled trials evaluating the clinical outcomes of patients receiving intra-articular injections of either HA or PRP were included as eligible studies. Two independent investigators assessed the selected studies and evaluated their risk of bias. Primary outcome measures included the Visual Analog Scale (VAS) score, the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score, and other relevant assessment indices. Dichotomous variables were analyzed using risk ratios (RR) with 95% confidence intervals (CI). Data analysis was conducted using RevMan software (version 5.3). RESULTS: A total of forty-two randomized controlled trials were included in this meta-analysis. No significant differences were observed between the patient populations in the two groups. The analysis demonstrated that PRP resulted in lower VAS and WOMAC scores compared to HA. Additionally, PRP exhibited superior performance across other evaluation indices. Notably, the incidence of adverse events was higher in the PRP group
however, all reported complications were mild. CONCLUSIONS: Based on the current evidence, intra-articular injection of PRP appears to be more effective than HA for the treatment of KOA, as indicated by the analysis of VAS, WOMAC scores, and other evaluation indices. TRIAL REGISTRATION: Retrospectively registered.