OBJECTIVES: Although several hemostats are available, drawbacks include limitations with efficacy and ease-of-use.  Despite their use, uncontrolled bleeding still remains common and is associated with important clinical and economic burden.  A study was conducted to estimate the economic impact of a novel fibrin sealant matrix (EVARREST^®) versus standard of care (SoC) in problematic severe soft tissue surgical bleeding in Italy. METHODS: An economic model quantified 30-day cost impact of EVARREST^® from an Italian hospital perspective.  Severe soft tissue bleeding trial resources included quantity of initial treatment, re-treatment, surgery time, transfusion risk, amount transfused, and hospitalization (including ICU and ward stay).  SoC was composed of Surgicel^® (88%) and conventional methods (e.g., manual compression).  The surgical analysis included resources clinically related to the significant hemostasis benefit of EVARREST^®vs. SoC (i.e., initial and re-treatment, operating time, transfusion). A hospital analysis included all resources collected. Published data on Italian costs were applied to resource use. A subgroup analysis was conducted for patients meeting coagulopathic criteria based on abnormal values for at least one of the trial coagulation parameters collected. RESULTS: The surgical base-case analysis predicted that EVARREST^® cost was offset by averted resource use with per patient cost impact of €1,016 vs. SoC. The hospital analysis predicts further resource reduction with EVARREST^® leading to cost-savings of €708 per patient.  In coagulopathic patients, the results dramatically improved, with the surgical and hospital analysis both showing cost-savings of €2,366 and €6,128, with EVARREST^®vs. SoC respectively.   CONCLUSIONS: In problematic bleeding situations, EVARREST^® may result in important cost savings for hospitals, in addition to meeting an important unmet need. This analysis suggests results may depend on surgical bleeding type, with increased benefit seen in challenging (i.e., coagulopathic) bleeding patients. Further study is needed to confirm findings.