Objective: To determine whether epsilon-aminocaproic acid (EACA) load of 50 mg∙kg-1 before skin incision, and infusion of 25 mg∙kg-1∙h-1 until skin closure during cranial vault reconstruction (CVR) were associated with decreased estimated blood loss and transfusion requirements.Background: Antifibrinolytic medications decrease bleeding and transfusion requirements during cardiothoracic and orthopedic surgeries with high blood loss, but practical reductions in blood loss and transfusion requirements have not been consistently realized in children undergoing CVR. Current dosing recommendations are derived from adult extrapolations, and may or may not have clinical relevance.Method: Retrospective case-controlled study of 45 consecutive infants and children undergoing primary craniosynostosis surgery at Covenant Children's Hospital during years 2010-2014. Exclusion criteria included revision surgery, and chromosomal abnormalities associated with bleeding disorders. Blood loss and blood transfusion volumes as a percent of estimated blood volume were compared in the presence of EACA while controlling for age, suture phenotype, use of bone grafting, and length of surgery. Secondary outcomes measures included volume of crystalloid infused, length of hospital stay, and any postoperative intubation requirement.Results: When analyzed based on length of surgery, EACA did reduce blood loss and blood transfusion (R2=0.19, P=.005 and R2=0.18, P=.010, respectively) with shorter surgeries.Conclusions and Relevance: Using a standardized dosing regimen of EACA during craniosynostosis surgery, we found statistical significance in blood loss and transfusion requirements in surgeries of the shortest duration. We suspect this may be due to our selected dosing regimen, which may be lower than recently recommended. This study contributes to the growing body of evidence supporting EACA in CVR for craniosynostosis. [ABSTRACT FROM AUTHOR]