Use of antifibrinolytic drugs in craniofacial and orthognathic surgery seems quite promising and has strong advocates. However, supporting evidence is controversial and limited by a small sample of individual studies. We sought to systematically review and meta-analyze the available data regarding the role of preoperative or intraoperative antifibrinolytic drugs (eg, tranexamic acid, aprotinin, or aminocaproic acid) in craniofacial and orthognathic surgery.We searched PubMed, Scopus, Embase, the Cochrane Library, and Web of Science through April 19, 2018, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Outcomes of interest included the volume of blood loss, volume of transfusions, and operative time. A meta-analysis was performed with a random-effects model using Review Manager (RevMan) software (The Cochrane Collaboration, Copenhagen, Denmark).We identified 32 eligible studies with 749 patients undergoing craniofacial surgery and 546 undergoing orthognathic surgery. Meta-analysis showed that antifibrinolytic use led to statistically significant decreases in blood loss and blood transfusions for craniofacial procedures in adult or pediatric patients and to significantly less blood loss during orthognathic surgical procedures. Operative time did not significantly differ for either type of surgery.Antifibrinolytics can significantly reduce blood loss in craniofacial surgical procedures including pediatric craniosynostosis and adult rhinoplasties and in orthognathic surgical procedures, as well as transfusion requirements in pediatric craniofacial surgical procedures. However, the clinical significance of the medications is still questionable because of the relative paucity of information on adverse effects and the usual small volume loss during those operations.