To evaluate effectiveness, in terms of patient-reported outcome measures, of platelet-rich plasma (PRP) injections for knee osteoarthritis compared to placebo and other intraarticular treatments.PubMed, Cochrane Library, Scopus, Embase, Web of Science, as well as the gray literature were searched on January 17, 2020. Randomized controlled trials (RCTs) comparing PRP injections with placebo or other injectable treatments, in any language, on humans, were included. Risk of bias was assessed following the Cochrane guidelines; quality of evidence was graded using the GRADE guidelines.Thirty-four RCTs, including 1403 knees in PRP groups and 1426 in control groups, were selected. WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) score favored PRP, with a statistically and clinically significant difference versus placebo at 12-month follow-up (P = 0.02) and versus HA (hyaluronic acid) at 6-month (P < 0.001) and 12-month (P < 0.001) follow-ups. A clinically significant difference favoring PRP versus steroids was documented for VAS (Visual Analogue Scale) pain (P < 0.001), KOOS (Knee Injury and Osteoarthritis Outcome Score) pain (P < 0.001), function in daily activities (P = 0.001), and quality of life (P < 0.001) at 6-month follow-up. However, superiority of PRP did not reach the minimal clinically important difference for all outcomes, and quality of evidence was low.The effect of platelet concentrates goes beyond its mere placebo effect, and PRP injections provide better results than other injectable options. This benefit increases over time, being not significant at earlier follow-ups but becoming clinically significant after 6 to 12 months. However, although substantial, the improvement remains partial and supported by low level of evidence. This finding urges further research to confirm benefits and identify the best formulation and indications for PRP injections in knee OA.