10 randomized controlled trials including 1096 overweight (BMI ≥ 25) patients diagnosed with knee osteoarthritis (OA) were included in this meta-analysis comparing hyaluronic acid (HA) and platelet-rich plasma (PRP) intra-articular injections. The primary outcome of interest was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score and associated sub-scores (pain, stiffness, and physical function). The secondary outcomes of interest included the following: International Knee Documentation Committee (IKDC) subjective score, pain on a Visual Analogue Score (VAS), and EuroQoL (EQ) on a Visual Analogue Scale (VAS). All outcomes were measured at 3, 6, 12 months except IKDC scores, which were measured at 2, 6, and 12 months follow-up. The pooled results revealed that WOMAC total and stiffness scores were both statistically significantly in favour of PRP at all timepoints. Pooled WOMAC pain scores were statistically significantly in favour of PRP at 6 and 12 months follow up (p=0.01, p=0.002; respectively). WOMAC physical function was statistically significantly in favour of PRP at 3 months (p < 0.00001), 6 months (p=0.06) and 12 months (p=0.003). Furthermore, pooled VAS pain scores (p=0.02) and EQ-VAS scores (p=0.001) were statistically significantly in favour of the PRP group at 12 months follow-up. Finally, pooled IKDC scores were not statistically significantly different between the two treatments at all timepoints.