Background: Acute coronary syndromes account for half of all deaths secondary to cardiovascular disease and represent a significant economic burden in the United States. Therefore, assessing hospitalization costs relative to Medicare reimbursement for these patients is important in understanding the impact of these patients on hospitals. We hypothesized that hospitalization costs for acute myocardial infarction patients treated with percutaneous coronary intervention (PCI) were higher than their associated Medicare payments. Methods: Using the Nationwide Inpatient Sample, we evaluated hospitalization costs for patients treated with PCI from 2001 through 2009 by multiplying hospital charges by the group average cost-to-charge ratio for each patient's hospitalization. Primary end points examined were total hospital costs and trends over time, which were correlated with clinical outcomes and insurance payments. Conclusions: Hospitalization costs for patients treated with PCI have been stabilizing over the last few years; however, there still remains a significant disparity between Medicare reimbursements and hospitalization costs, which has potential implications on patient outcomes, quality of care, and hospital sustainability.