While platelet rich plasma (PRP) has been extensively studied in treating osteoarthritis (OA), there has been an ongoing debate regarding the efficacy of PRP and the optimal subpopulation for PRP treatment remains unknown. We hereby aim to establish a pharmacodynamic model-based meta-analysis (MBMA) to quantitatively evaluate PRP efficacy, comparing with hyaluronic acid (HA) and identify relevant factors that significantly affect the efficacy of PRP treatment for OA.We searched for PubMed and Cochrane Library Central Register of Controlled Trials of PRP randomised controlled trials (RCTs) for the treatment of symptomatic or radiographic OA from the inception dates to July 15, 2022. Participants' clinical and demographic characteristics and efficacy data, defined as Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and visual analog scale (VAS) pain scores at each time point were extracted.A total of 45 RCTs (3,829 participants) involving 1,805 participants injected with PRP were included in the analysis. PRP reached a peak efficacy at approximately 2 to 3 months after injection in patients with OA. Both conventional meta-analysis and pharmacodynamic maximal effect models showed that PRP was significantly more effective than HA for joint pain and function impairment (additional decrease of 1.1, 0.5, 4.3 and 1.1 scores compared to HA treatment at 12 months for WOMAC pain, stiffness, function and VAS pain scores, respectively). Higher baseline symptom scores, older age (≥60 y), higher body mass index (BMI) (≥30), lower Kellgren-Lawrence (K-L) grade (≤2) and shorter OA duration (<6 mo) were significantly associated with greater efficacy of PRP treatment.These findings suggest that PRP is a more effective treatment for OA than the more well-known HA treatment. We also determined the time when the PRP injection reaches peak efficacy and optimised the targeting subpopulation of OA. Further high-quality RCTs are required to confirm the optimal population of PRP in the treatment of OA.Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.