Objective: Fibrin sealants are used in a variety of surgical procedures to reduce wound bleeding. This may consequently decrease hospital costs and lengths of stay (LOS). This study sought to compare costs and LOS following fibrin sealant use during spinal surgery. Methods: Data were extracted from a large U.S. hospital-based, service-level comparative database. Procedures were identified using principal ICD-9 codes. Patients who received either FloSeal® only or one of two comparison products (Gelfoam®+thrombin or Surgicel®+thrombin) and were discharged from hospital between April 1, 2003 and September 30, 2006 were included. Costs were considered from the hospital perspective and were derived from either reported actual costs or an estimated calculation of costs-to-charges from the Medicare Cost Report. Regression modeling with log transformation was employed to compare differences in fixed hospital costs (those insensitive to volume), variable costs (those sensitive to volume), and post-operative LOS. Control variables included age, gender, All Patient Refined-Diagnosis Related Group severity codes, region, hospital teaching status, bed size, population served (urban or rural), and primary payer. Results: A total of 82,788 discharges were included. The models demonstrated that patients who received Gelfoam+thrombin had higher fixed and variable costs (+6.1% and +7.3%, respectively, p<0.01) and Surgicel+thrombin patients had higher fixed and variable costs (+18% and +10%, p<0.01, respectively) compared to FloSeal only. In terms of fixed costs, the predicted increase was $15,956 for Gelfoam+thrombin and $18,639 for Surgicel+thrombin patients. In terms of variable costs, the predicted increase was $25,413 per Gelfoam+thrombin and $24,909 per Surgicel+thrombin patient. Surgicel+ thrombin patients also had higher (+6%, p<0.01) post-operative LOS compared to FloSeal patients. Conclusion: FloSeal demonstrated significant cost reductions and post-operative LOS, compared to other commonly-used products. Limited prospective reimbursements based on a DRG system make it necessary for health care providers to consider more cost-effective surgical aids for spinal surgeries.