PurposeTo assess the effectiveness of viscosupplementation or platelet-rich plasma (PRP), compared to standard care, for pain relief after knee arthroscopic debridement in patients with meniscal pathology and osteoarthritis (OA), under normal clinical practice conditions.Patients and methodsWe conducted a prospective, randomized, evaluator-blind, pilot study. After arthroscopy, patients were randomized to receive 1) five injections of HA1 (Suprahyal®/Adant®); 2) four injections of HA2 (Orthovisc®); 3) three injections of HA3 (Synvisc®); 4) a single injection of PRP (GPS™ II); or 5) standard care (control). Patients were followed up for 18 months. Clinical outcomes were evaluated using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) at 3, 6, 12, and 18 months. Minimally Clinical Important Improvement (MCII), as relative improvement ≥20 for pain and function, was also calculated.ResultsFifty patients were included. At early follow-up (3 months), total WOMAC scores improved in all groups compared to baseline with reductions of 44.79% (HA1), 24.02% (HA2), 40.38% (HA3), 39.77% (PRP), and 27.64% (control) (p=0.002 HA1 compared to HA2). At 18 months, the higher improvement in total WOMAC was in HA1 with a 65.20% reduction, followed by PRP (55.01%), HA3 (49.57%), and HA2 (29.82%), whereas the control group had a 14.55% increase over baseline (p=0.001 control compared to HA1 and HA3). The percentage of patients achieving the MCII for both pain and function at 18 months was 100% (HA1), 80% (HA3), 60% (HA2), and 60% (PRP), whereas, in the control group, all patients returned to pre-arthroscopy levels. There were no adverse events attributable to surgery or to intraarticular administration.ConclusionViscosupplementation following arthroscopy is more effective than PRP in adequately selected patients with meniscal lesions occurring concomitantly with OA. Further controlled studies with a larger sample size and/or alternative regimens would be of interest for the scientific community.