BackgroundLateral ankle sprains are common among active individuals and, if not managed properly, can result in recurrent sprains, chronic instability, and post-traumatic ankle osteoarthritis. Standard treatment includes physical therapy and a brief period of rest, followed by early functional rehabilitation. Autologous platelet-rich plasma, which is rich in growth factors, has demonstrated promising healing responses in acute ankle sprains. This systematic review assessed the current evidence regarding the efficacy and adverse events associated with autologous PRP injection in acute ankle sprain injuries.MethodThis systematic review adhered to PRISMA guidelines. An electronic search was performed across PubMed, Embase, Scopus, and Cochrane Library using specific keywords. Eligible studies comprised prospective or retrospective comparisons of autologous PRP injection versus control for acute ankle sprain injuries reported in English.ResultsThree randomized controlled trials and one prospective comparative study met the inclusion criteria, involving 85 ankle injuries in 84 autologous PRP injection groups and 57 ankle injuries in 56 patients in the control group. Autologous PRP injection provided superior short-term pain relief, functional outcomes, and an earlier return to activity and sports, as well as improved radiological outcomes compared to the control group. However, during the follow-up period, both groups exhibited comparable results in terms of Visual Analog Scale (VAS) scores and functional outcomes, with no reported adverse events. A meta-analysis of limited data for VAS and American Orthopaedic Foot and Ankle Society scores demonstrated comparable outcomes between the two groups.ConclusionAutologous PRP injection appears to play a beneficial role in acute ankle sprains by reducing pain, expediting return to play, and enhancing function, with no reported adverse events.