OBJECTIVES: Bleeding during complex cardiac surgery is associated with several negative clinical outcomes. Fibrinogen concentrate (FC) is a coagulation factor concentrate that may positively affect these clinical outcomes. The objective of this study was to compare health economic outcomes between using a hemostatic therapy protocol with FC and a protocol without FC during complex cardiac surgery. METHODS: The input data of the model was based on a systematic literature search, and interviews with experts. Costs were retrieved from national databases. The primary effectiveness parameters were the number of blood transfusions avoided and the amount of blood loss avoided. One-way and probabilistic sensitivity analyses (PSA) were performed to test the robustness of results.  RESULTS: Five studies were included, representing 143 patients. The incremental costs per blood transfusion avoided were €63 and per unit blood loss avoided €2.4. The average number of blood transfusions reduced with 10 units per patient [95% CI: 8 - 12] and blood loss with 391mL/12hrs [95%CI: 81mL/12hrs – 711mL/12hrs] in the with FC protocol compared to the without FC protocol, whilst costs slightly increased (+€611 [95%CI: €-2,210 - €3,399]). The FC protocol reduced the number of blood transfusions and blood loss in 100% of the simulations of the PSA, and reduced these clinical outcomes and costs in 33.3%. The FC dosage was the main cost driver in the model. The FC protocol would be cost-saving if lower FC dosages were used (e.g. 2 or 4 grams instead of 6.4 grams), or if costs of side effects were included (transfusion related lung injury and renal failure). CONCLUSIONS: Our study indicates that a hemostatic therapy protocol with FC is cost-effective in complex cardiovascular surgery, leading to better clinical outcomes with minimal incremental costs. Future studies need to provide clinical evidence that a lower dosage of FC will still suffice to ensure similar health outcomes.