The Angio-Seal vascular closure device has been shown to be safe and effective in decreasing the time to hemostasis after percutaneous coronary intervention (PCI). The health economic implications of routinely using Angio-Seal after PCI have not been explored. We performed a cost-minimization analysis comparing routine Angio-Seal use after PCI with mechanical compression using a decision analytic model. The relative probabilities of 7 vascular access complications were derived from pooled analysis of published randomized trials. The incremental hospital cost of each vascular complication was estimated by a matched case-control analysis of 3,943 patients who underwent PCI at our center from January 2002 and December 2004. Appropriate sensitivity and uncertainty analyses were performed. After accounting for differences in expected rates of specific complications between the 2 strategies and the incremental costs of each vascular event, the routine use of Angio-Seal was associated with a lower cost per PCI procedure of 44 dollars. Probabilistic sensitivity analysis of all model assumptions using second-order Monte Carlo simulation confirmed the economic advantage of Angio-Seal in 74% of model replications. In conclusion, after PCI, the routine use of Angio-Seal for femoral vascular access management was associated with net cost savings compared with mechanical compression. This cost savings was in addition to the previously demonstrated advantages of Angio-Seal in terms of patient comfort and preference.