OBJECTIVES: Recent literature suggests complication rates associated with current Vascular Closure Devices (VCDs) are comparable or reduced when compared to manual compression. However, well-documented differences exist among VCDs regarding the type and frequency of complications. A recent global budget impact model based on a naïve indirect treatment comparison (ITC) estimated the cost-savings associated with use of the VCD EXOSEALTM vs. AngiosealTM, StarcloseTM, PercloseTM and MynxTM from the US hospital perspective. Based on this ITC, the analysis was adapted to Italy and Spain from the National Health System (NHS) perspective over a 1 year time horizon. METHODS: The ITC was used to calculate the incidence of reinterventions (i.e. amputation (AM), vascular surgery (VS), endovascular procedure (EP), transfusion (TR) and ultrasound guided interventions (UGI)) following complications associated with each VCD.  The annual number of VCDs used and costs of reinterventions were obtained from local databases. The means and 95% confidence intervals (95%-CI) for the budget impact were estimated using bootstrap methods (1.000 simulations) assuming 100% use of ExosealTM vs. 100% use of another VCD, and 100% use of Exoseal vs.  2010 VCD market-share for percutaneous coronary interventions (PCI) procedures. Device acquisition costs were assumed identical. RESULTS: Savings per procedure with EXOSEALTM (Italy/Spain) would be approximately of (22,8€/11,9€) vs.  AngiosealTM, (15,5€/13,5€) vs. StarcloseTM, (83,1€/72,6€) vs. PercloseTM  and (11,2€/16,4€) vs.  MynxTM. Considering  90.239 and 37.064 annual PCI procedures with VCDs in Italy and Spain respectively (1 VCD per procedure), 100% use of EXOSEALTM vs. combined use of VCDs could save 2.680.870€ (95%-CI: 2.538.334€ – 2.823.405€) for the Italian NHS and 797.070€ (95%-CI: 734.231€ – 859.909€) for the Spanish NHS. CONCLUSIONS: This analysis suggests use of EXOSEAL™ in patients undergoing PCI procedures may result in important cost-savings for the Italian and the Spanish NHS. Additional data will be required to confirm low complication rates with EXOSEAL™.