Platelet-rich plasma (PRP) is a promising noninvasive technique for facial rejuvenation. This systematic literature review aims to appraise the nature and quality of published evidence evaluating the effectiveness and safety of PRP in facial rejuvenation.A systematic literature review was conducted with the search string "Platelet-rich plasma AND Facial rejuvenation" in PubMed and Embase. Clinical studies evaluating the outcomes after PRP-based facial rejuvenation either as monotherapy or in combination with other treatment modalities were included. Studies evaluating wound-healing properties of PRP were excluded. The outcomes included both patient-reported and physician-assessed outcomes. Nonstatistical synthesis of evidence was performed by qualitative assessment. The results are reported by the Synthesis Without Meta-analysis (SWiM) reporting standard.A total of 36 studies that included a total of 3172 patients were considered for the evidence synthesis. The number of patients in the included studies ranging from 11 to 2005 with a median of 27.5 patients that reflects the challenges in clinically assessing the aesthetic outcomes after PRP-based facial rejuvenation. Among the 36 studies, 17 were observational studies and 18 were interventional studies with 1 being case report PRP was evaluated either alone or in combination with hyaluronic acid, lipofilling, micro-needling technique, and laser-based interventions. Among the studies, 1 study reported the enhanced platelet concentrate in a fibrin matrix to be relatively safe and effective with a maximum benefit observed at 12 weeks suggesting the platelet-rich fibrin matrix may provide desired aesthetic outcomes and it requires further studies to substantiate.The results suggest very limited clinical evidence, and further clinical studies are warranted to establish the effectiveness of PRP in facial rejuvenation. Furthermore, a consensus for end points used for establishing clinical utility in patients requiring facial rejuvenation is warranted.© 2021 Xiao et al.