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Objective: 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. The authors hereby aim to establish a pharmacodynamic model-based meta-analysis to quantitatively evaluate PRP efficacy, comparing with hyaluronic acid (HA) and identify relevant factors that significantly affect the efficacy of PRP treatment for OA. Methods: The authors searched for PubMed and the Cochrane Library Central Register of Controlled Trials of PRP randomized controlled trials (RCTs) for the treatment of symptomatic or radiographic OA from the inception dates to 15 July 2022. Participants' clinical and demographic characteristics and efficacy data, defined as Western Ontario and McMaster Universities Osteoarthritis Index and visual analog scale pain scores at each time point were extracted. Results: A total of 45 RCTs (3829 participants) involving 1805 participants injected with PRP were included in the analysis. PRP reached a peak efficacy at ~ 2-3 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 Western Ontario and McMaster Universities Osteoarthritis Index pain, stiffness, function, and visual analog scale pain scores, respectively). Higher baseline symptom scores, older age (=60 years), higher BMI (=30), lower Kellgren-Lawrence grade (=2) and shorter OA duration (< 6 months) were significantly associated with greater efficacy of PRP treatment. Conclusion: These findings suggest that PRP is a more effective treatment for OA than the more well-known HA treatment. The authors also determined the time when the PRP injection reaches peak efficacy and optimized the targeting subpopulation of OA. Further high-quality RCTs are required to confirm the optimal population of PRP in the treatment of OA. [ABSTRACT FROM AUTHOR]