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Blood loss is the leading cause of mortality after major craniofacial surgery. Autologous blood donation, short-term normovolemic hemodilution, and intraoperative blood salvage have shown low efficacy in decreasing transfusions. Tranexamic acid (TXA) is a synthetic antifibrinolytic drug that competitively decreases the conversion of plasminogen to plasmin, thereby suppressing fibrinolysis. The purpose of this study was to investigate the impact that TXA administration has on intraoperative blood loss and blood product transfusion in pediatric patients undergoing cranial vault reconstruction.An Internal Review Board-approved retrospective study was conducted on a consecutive series of pediatric patients undergoing cranial vault reconstruction from January 2009 to June 2012. Seventeen consecutive patients who received TXA at the time of cranial vault reconstruction were compared with 20 patients who did not receive TXA. Criteria for blood product transfusion were identical for both groups. Outcomes including perioperative blood loss, volume of blood transfused, and adverse effects were analyzed.The TXA group had a significantly lower perioperative blood loss (9.4 versus 21.1 mL/kg, P < 0.0001) and lower volume of perioperative mean blood product transfusion (12.8 versus 31.3 mL/kg, P < 0.0001) compared with the non-TXA group. There was no significant difference in demographic data, infection rate, change in preoperative to postoperative hematocrit, duration of surgery, or complication rates between the TXA and non-TXA groups. No drug-related adverse effects were identified in patients who received TXA.The use of TXA in pediatric cranial vault reconstruction significantly reduces perioperative blood loss and blood product transfusion requirements. The TXA administration is safe and may improve patient outcomes by decreasing the likelihood of adverse effects related to blood product transfusion.