Abstract / Summary
Importance: Knee osteoarthritis is among the leading causes of pain-related disability in adults, and intra-articular injection occupies an established niche between conservative management and arthroplasty. Platelet-rich plasma (PRP) and hyaluronic acid (HA) are both in widespread clinical use, yet which agent should be preferred, and for which patients, remains unsettled. Aim or objective: The efficacy and safety of intra-articular PRP were compared with those of intra-articular HA for pain and physical function in adults with symptomatic knee osteoarthritis, and study-level modifiers of the treatment effect were identified. Evidence review: PubMed/MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception to April 14, 2026, without language or date restrictions, supplemented by reference-list searching. Randomized controlled trials comparing intra-articular PRP with intra-articular HA in adults with knee osteoarthritis and reporting the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score or the pain visual analog scale (VAS) at 4 weeks or later were eligible. Two reviewers independently screened, extracted data, and appraised each trial with the Cochrane Risk of Bias 2.0 tool. Mean differences (MDs) were pooled using random-effects models; heterogeneity was explored through prespecified subgroup analyses (PRP leukocyte content, injection number, osteoarthritis severity, follow-up duration), sensitivity analyses, and meta-regression; and certainty of evidence was rated using the Grading of Recommendations Assessment, Development and Evaluation approach. Findings: Twenty-eight randomized controlled trials comprising 2,685 participants were included. PRP was associated with greater improvement than HA in WOMAC total score (MD −8.14, 95% confidence interval [CI] −10.79 to −5.48; P < 0.00001; I 2 = 96%) and in pain VAS score (MD −7.89, 95% CI −12.90 to −2.89; P = 0.002; I 2 = 97%). Treatment effects were larger with leukocyte-poor PRP ( P -interaction = 0.04), with multiple-injection protocols ( P -interaction = 0.04), and in Kellgren–Lawrence grade I–II disease ( P -interaction = 0.03). Meta-regression confirmed osteoarthritis severity ( P = 0.03) and injection number ( P = 0.04) as statistically significant effect modifiers, together explaining approximately 24% of the between-study variance. Restricting the analysis to trials at low risk of bias and re-estimating the between-study variance with the restricted maximum likelihood estimator attenuated but did not nullify the advantage of PRP. Egger's test showed no statistically significant funnel plot asymmetry (WOMAC P = 0.21; VAS P = 0.24). Certainty of evidence was moderate for WOMAC and low for VAS. Conclusion and Relevance: Intra-articular PRP produced greater functional improvement than HA with moderate certainty and greater pain relief with low certainty. The largest benefit is to be expected in mild-to-moderate disease treated with leukocyte-poor PRP in a multiple-injection protocol, and this profile should inform patient selection. HA remains a reasonable alternative, and standardized PRP preparation and reporting are required before firmer recommendations can be made. Level of evidence: Level I, systematic review and meta-analysis of randomized controlled trials. PROSPERO registration: CRD420261413006.