The antifibrinolytic drug tranexamic acid (TXA) is effective in reducing blood loss and transfusion requirements in other fields of elective surgery and its use is emerging in a number of plastic surgical subspecialties. This systematic review and meta-analysis evaluates the current evidence for the efficacy and safety of TXA in craniomaxillofacial, head and neck, breast, aesthetic, burns, and reconstructive microsurgery. We searched PubMed, EMBASE, Medline, The Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials for randomized controlled trials of TXA in plastic surgery. Studies were analyzed using standard methodology. A total of 7965 records were screened, of which 14 met the inclusion criteria. Seven were suitable for meta-analysis. In craniofacial surgery, TXA was associated with a mean reduction in blood loss of 18.2 mL/kg (P = 0.00001) and a mean reduction in blood transfusion of 8.7 mL/kg (P = 0.0001). In orthognathic surgery, TXA was associated with a mean reduction in blood loss of 156 mL (P = 0.001). Tranexamic acid may also have a role in reducing drainage output volumes in oncological breast excision and lymph node dissection of the neck. Level-1 evidence for efficacy in aesthetic surgery, burns, and reconstructive microsurgery is lacking. Although no reported complications were attributable to TXA, there remain no phase IV trials published. Level-1 evidence supports the use of TXA in craniofacial and orthognathic surgery. There exists an unmet need for studies in areas, including burns, aesthetic surgery, and reconstructive microsurgery. Phase IV trials in areas of proven efficacy are also required.