The chances of extrusion of mineral trioxide aggregate (MTA) are quite high if apical barrier is not present in immature pulpless permanent teeth. Platelet-rich fibrin (PRF) enriched with platelets and growth factors serves to accelerate the wound healing of periapical lesion in immature pulpless permanent teeth and also serves as internal matrix to condense MTA.The aim of the present study was to comprehensively review the clinical success of MTA+PRF in healing of periapical lesions in immature pulpless permanent teeth.An electronic search for systematic review was conducted in Pubmed/Medline (www.ncbi.nlm.nih.gov), Cochrane (www.cochrane.org), Scopus (www.scopus.com) databases upto 15th January 2020 related to the healing of periapical lesions in permanent teeth with immature apices when combination of MTA+PRF was used. A sample of 10 relevant studies and case reports were identified in our search out of 65. The sampling method was simple random technique. The studies and case reports with Randomised Controlled Trials(RCTs), Invitro studies, Case reports and animal studies in healing of periapical lesion were included in our comprehensive systematic review.The search showed that the combination of MTA+PRF showed faster and definite periapical lesion healing in immature permanent teeth. The follow-up period was also recorded in all the relevant studies and case reports.Acclerated bone filling was seen in healing of periapical leions when MTA+PRF was used.