Blood transfusion is common in cranial vault surgery, and protocolized efforts to minimize transfusion have been reported in recent years. This study assesses the long term, prospective outcomes of a pediatric blood management protocol for the cranial vault reconstruction (CVR) population. Data from a retrospective control cohort and a prospective cohort employing a protocol for preoperative hematologic optimization of patients undergoing CVR from January 2015 to October 2023 was reviewed. Preoperative hemoglobin (Hgb) determined the preoperative protocol. Intraoperative tranexamic acid (TXA) and/or aminocaproic acid, cell-saver technology, and postoperative iron or erythropoietin alfa supplementation were also used in the protocol. For statistical analysis, P<0.05 was deemed significant. The cohort consisted of 194 successive patients (20 control and 174 treatment). Age, sex, and weight were not significantly different between groups. Mean postoperative Hgb was significantly higher in the control group (P<0.01). No difference was observed in Hgb at discharge between control and treatment groups. Mean estimated blood loss, volume of intraoperative packed red blood cells, rate of packed red blood cell transfusion, and mean total transfusion volume during hospitalization were significantly higher in the control group compared with the treatment group (P<0.01). Mean length of stay did not differ between groups. Efforts to optimize blood management in the CVR population are critical. This prospective study represents a robust and reproducible protocol for pediatric blood management with significant reductions in transfusion requirements.