The risk of post-inflammatory hyperpigmentation (PIH) in patients undergoing dermatologic procedures is well known. It is especially common after laser procedures and chemical peels but can be seen with any procedure. PIH is also a sequela of acne, burns, and other trauma. High-risk patients are thought to have excessive production and abnormal distribution of melanin within the skin that triggers PIH, but the exact pathophysiology is unknown.1 We define high-risk patients as Fitzpatrick skin types 3–5, those with existing PIH, or a history of PIH.1,2 Tranexamic acid (TXA) is an antifibrinolytic medication prescribed to treat bleeding and is also used off-label to treat melasma. TXA is contraindicated in patients with hypercoagulable conditions, renal impairment, vision impairment disorders, pregnancy, breast-feeding, or on hormone therapies.3,4,5 From 2015–2020, we have used TXA off-label to successfully treat and/or prevent PIH in approximately 82 high-risk patients after injuries or prior to procedures that disrupt the epidermis. We also have used TXA to prevent PIH after acute injuries such as irritant dermatitis, thermal burns, and abrasions. We now consider TXA treatment for all at risk patients prophylactically before undergoing microneedling, cryotherapy, cryolipolysis, chemical peels, and laser treatments. J Drugs Dermatol. 2021;20(3) doi:344-345. 10.36849/JDD.5622.