OBJECTIVES: Technological advances have enabled percutaneous coronary intervention (PCI) to be applied to expanding indications. However, escalating costs are of concern to patients, providers and payers. This study assessed the incremental medical costs of treating major in-hospital procedural complications incurred by patients undergoing PCI. METHODS: We considered all patients undergoing elective, urgent, or emergent PCI at Mayo Clinic Rochester between 3/1/1998-3/31/2003 in analyses. Clinical, angiographic, and outcome data were derived from the Mayo Clinic PCI Registry. In-hospital PCI complications included major adverse cardiac and cerebrovascular events (MACCE) (defined as death, myocardial infarction [MI], emergent coronary bypass surgery, repeat PCI, or stroke) and bleeding of clinical significance. Administrative data was used to estimate total costs (hospital and physician) in standardized, year 2004 constant-dollars. We used generalized linear modeling to estimate the incremental costs associated with complications adjusting for demographic, clinical, angiographic, and procedural characteristics. RESULTS: 1,071 (13.2%) of patients experienced at least one of the selected complications during hospitalization. Patients experiencing complications were older, more likely to present with emergent PCI, recent or prior MI, multi-vessel disease, B2/C type lesions, and comorbid conditions than patients who did not experience these events. Unadjusted total costs were, on average, $27,865 ± $39,424 for patients who experienced any complication compared to $12,279 ± $6,796 for those who were free of complications (p<0.0001). Adjusted mean total costs were $7,000 higher for patients experiencing complications compared with patients who were complication free (95% CI of cost difference: $5,854, $8,145). Incremental costs associated with only bleeding events, only MACCE, or for patients experiencing bleeding and MACCE events were $5,813, $5,151, and $15,699, respectively (p<0.0001). CONCLUSIONS: This observational study highlights the significant economic burden associated with in-hospital procedural complications. Interventions to reduce the risk of adverse events likely enhance financial as well as clinical performance.