Platelet-rich fibrin (PRF) consists of a matrix that provides the necessary elements for wound healing, acting as a biodegradable scaffold for cell migration, proliferation, and differentiation, in addition to the delivery of growth factors and angiogenesis. This study aims to determine the effectiveness of the autologous PRF in the treatment of wounds of different etiologies. We carried out a systematic review of randomized clinical trials, guided by the recommendations of the Cochrane Collaboration using the following databases: Pubmed/MEDLINE, EMBASE, Web of Science, and CENTRAL. The search strategy resulted in the inclusion of ten studies that evaluated the use of PRF dressings for the healing of acute or chronic wounds of multiple etiologies. Among the 172 participants treated with PRF in wounds of varying etiologies and different segment times, 130 presented favorable events with the use of the intervention. Among the 10 studies included, only two of them did not demonstrate better results than the control group. The studies showed clinical heterogeneity, making it impossible to perform a meta-analysis. The findings do not provide enough evidence to support the routine use of PRF dressings as the first line of treatment for the healing of acute or chronic wounds of different etiologies. There was great variability in the application of the various protocols and the ways to prepare the PRF, resulting in clinical heterogeneity. Therefore, it makes it impossible to synthesize and to collect evidence from different types of studies in the meta-analysis, which affects the results and their proper discussion.