Craniofacial surgery in infants still harbors the risk of significant blood loss and the need for red blood cell (RBC) transfusion. Hence, the aim of the present study was to investigate the antifibrinolytic effect of tranexamic acid (TXA) on intraoperative blood loss and RBC transfusion rates during fronto-orbital advancement (FOA) in isolated metopic synostosis. A total of 33 children with metopic synostosis were operated on using standardized FOA, of which 16 patients (48.5%) were treated without intraoperative TXA (non-TXA group) and 17 patients (51.5%) received TXA intraoperatively (TXA group). To accurately evaluate the calculated blood loss (CBL) we analyzed the values for pre- and postoperative hematocrit and the volume of the RBC transfusion. The mean CBL and the mean weight-adjusted CBL was significantly lower for patients receiving TXA compared with the non-TXA group (158.8 ml vs. 198.5 ml, p = 0.0001; and 19.1 ml/kg vs. 22.3 ml/kg, p = 0.0293, respectively). In addition, the mean RBC transfusion and the mean weight-adjusted RBC transfusion was significantly lower for the TXA group (252.2 ml vs. 280.0 ml, p = 0.0001; and 27.9 ml/kg vs. 31.3 ml/kg, p = 0.0345, respectively). The mean duration of the surgical procedure did not differ statistically between the groups (132 min vs. 136 min, p = 0.4081), hence the lower CBL in the TXA-group was not related to a shorter cutting–suture time. As the use of intraoperative TXA minimizes blood transfusion volumes in children who undergo FOA, antifibrinolytics, such as TXA, should be considered for routine use in pediatric craniofacial surgery.