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Sahar Hasan Alsharif,1 Asail Saeed Alghamdi,2 Zahraa Ali Alwayel,3 Saeed Nasser Alaklabi,4 Nawras Ali Alyamani,5 Mohamad Abdulwahab Sabsabee,6 Dunya Ali Abdulathem Bu izran,3 Abdulmajeed M Alajlan1 1Department of Dermatology, King Saud University, Riyadh, Saudi Arabia; 2Department of Medicine, Albaha University, Albaha, Saudi Arabia; 3Department of Medicine, King Faisal University, Al Ahsaa, Saudi Arabia; 4Department of Medicine, Bisha University, Bisha, Saudi Arabia; 5Department of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia; 6Department of Medicine, Sulaiman Al Rajhi University, Qassim, Saudi ArabiaCorrespondence: Sahar Hasan Alsharif, Department of Dermatology, King Saud University, P.O. Box 24353, Riyadh, 11322, Saudi Arabia, Tel +00966555539141, Email S.H.Alsharif@hotmail.comBackground: Post-inflammatory hyperpigmentation (PIH) is skin hyperpigmentation that occurs due to any inflammatory condition. Triggering the melanocytes by inflammation leads to melanin overproduction and deposition. Tranexamic acid (TXA) is an antifibrinolytic medication prescribed to treat bleeding. Recently, there are some studies about the use of TXA in the treatment of PIH.Objective: The aim of this study is to identify the efficacy and the best mode of delivery for tranexamic acid in the treatment of PIH.Methods: This systematic review is reported in accordance with PRISMA guidance. We included all relevant English-language studies that were published up to September 2022 in the following electronic databases: Cochrane Library, PubMed, Embase, and Google Scholar. The initial search yielded 61 articles, 9 of which were included after applying inclusion and exclusion criteria.Results: The systematic review included a total of 196 patients who were over the age of 16 years old. Tranexamic acid was delivered orally in 4 studies, topically in 2 studies, and both simultaneously in 1 study. In addition, intradermal injection was used in 2 other studies. Almost all studies advocated the use of all routes for accelerating the clearance of hyperpigmentation with more favor towards topical and intradermal routes due to their mild reported side effects when compared to oral routes.Conclusion: Intradermal TXA is considered the best route, which exhibits fewer side effects with less cost and excellent outcomes, while oral TXA is found to be less preferable than other routes due to the incidence of undesirable adverse events.Keywords: tranexamic acid, post-inflammatory hyperpigmentation, TXA, PIH, efficacy