Introduction: PRP is gaining increasing interest for pain relief and improvement of joint function in patients with knee osteoarthritis (KOA) but practices and results remain heterogeneous limiting its adoption as standard of care. Current international recommendations are to collect real-life evidence of efficacy with a systematic monitoring of PRP quality and patients' outcomes. We aimed to analyze the response of patients presenting KOA and treated with standardized PRP injection in routine care. We also investigated the potential contributing factors including patient's phenotype and PRP characteristics. Methods: Patients with symptomatic KOA and that failed first-line therapy received a single injection of a qualified PRP prepared using medical devices allowing to recover a high/very high volume of very pure PRP. Visual analogue scale (VAS) and Western Ontario and McMaster Osteoarthritis Index (WOMAC) score were recorded at baseline and during 18 months follow-up. Results: 431 patients had available follow-up data at 3 months, 291 at 6 months, 137 at 12 months and 44 at 18 months. PRP induced a significant decrease of WOMAC score at all follow up endpoints (29.2 +/- 19.2 at 3 months, p < 0.001 and 25.9 +/- 19.7 at 12 months, p < 0.01, compared to 39.7 +/- 18.9 at baseline). Similar results were observed for pain VAS (38.9 +/- 23.3 at 3 months, p < 0.001 and 35.3 +/- 24.1 at 12 months, p < 0.05, compared to 56.0 +/- 20.7 at baseline). Changes at 12 months were correlated to baseline scores and to the level of improvement at 3 months. The proportion of OMERACT OARSI responders reached 56.2 % for the total cohort and 60.4 % for severe patients at 6 months. Treatment failure occurred for 8.4 % of patients. Age, BMI or Kellgren-Lawrence grade did not impact on efficacy. Conclusion: This real-life study evidences the clinical benefit of a standardized high or very high-volume injection of very pure PRP in patients with KOA, including those with a severe grade. It opens perspectives in the positioning of such strategy to delay arthroplasty and provide insights on factors able to anticipate long term efficacy.