Twenty-six randomized controlled trials including 2430 adults with knee osteoarthritis (OA) were included in this meta-analysis comparing platelet-rich plasma (PRP) injections and hyaluronic acid (HA) injections for the relief of symptoms. Pooled outcomes of interest included the incidence of adverse events, the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index, pain, stiffness, and physical function scores, pain scores on a Visual Analogue Scale (VAS), Euro-QoL scores on a VAS (EQ-VAS), International Knee Documentation Committee (IKDC) scores, Tegner activity scores, Lequesne scores, Knee Injury and Osteoarthritis Outcomes Scores (KOOS) for pain, symptoms, daily activity, sport, and quality of life, and patient satisfaction. In addition, WOMAC scores, VAS scores, EQ-VAS scores and IKDC scores were pooled at 1, 3, 6 and 12 months post-treatment, whilst Tegner scores and KOOS scores were pooled at 2, 6 and 12 months post-treatment. Adverse events and satisfaction at final follow-up were pooled. Pooled results revealed statistically significantly favourable WOMAC total scores, WOMAC physical function scores, and VAS pain scores in the PRP group compared to the HA group at 3, 6 and 12 months post-treatment (p<0.05 for all). Pooled WOMAC pain scores, WOMAC stiffness scores, EQ-VAS scores, and IKDC scores were statistically significantly in favour of the PRP group at 6 and 12 months post-treatment (p<0.05 for all). Moreover, pooled Tegner scores at 12 months were statistically in favour of the PRP group (p=0.04). In the remaining pooled outcomes, no statistical significant differences were observed between the two groups.