Inhibition of platelet aggregation with glycoprotein (GP) IIb-IIIa receptor blockers has been shown to reduce ischemic complications in patients with acute coronary syndromes (ACS) and in those undergoing percutaneous coronary intervention (PCI) in multiple placebo-controlled, randomized clinical trials. The effect of pharmacologic and cost differences between abciximab and eptifibatide, the only GP IIb-IIIa inhibitors indicated for PCI, on clinical outcomes and total hospital costs for patients undergoing PCI remain to be defined. To determine the rate of clinical events and costs associated with the use of abciximab vs eptifibatide at our centers, we retrospectively reviewed data for the cohort of 188 consecutive patients who underwent PCI and were treated with either abciximab (n = 85) or eptifibatide (n = 103) in the period between January 1998 and June 1999. The choice of a GP IIb-IIIa inhibitor was based on the preference of the interventional cardiologist. In-hospital events evaluated included death, major bleeding, minor bleeding, and hematoma. Additionally, the duration of hospital stay and total in-hospital costs were also assessed. Clinical events at 6 months included combined incidence of death, acute myocardial infarction (MI), or unstable angina (UA), as well as the incidence of hospital readmissions. In-hospital complications were generally more common with abciximab (death: 4.7% vs 0% with eptifibatide; major bleeding: 7.1% vs 4.8%, respectively; minor bleeding: 9.4% vs 5.7%, respectively; hematoma: 21.2% vs 21.4%, respectively), although none of these differences reached statistical significance. However, abciximab therapy was associated with a significantly longer mean duration of hospitalization (4.17 ± 0.48 days vs 2.85 ± 0.26 days with eptifibatide; P = 0.017) and a significantly higher mean total in-hospital costs ($31,396 ± 2,111 vs $25, 135 ± 815; P = 0.007). At six-month follow-up, the combined incidence of death, acute MI, or UA was also significantly higher in the abciximab group (32.9% vs 15.5%; P = 0.01). Additionally, hospital readmissions related to acute coronary syndromes at 6 months occurred significantly more often in the abciximab group (36.7% vs 16.5% with eptifibatide; P = 0.014). Our retrospective analysis of 188 patients undergoing PCI indicates that the use of eptifibatide instead of abciximab is associated with significantly lower in-hospital costs, significantly shorter duration of index hospitalization, and significantly reduced rates of ischemic complications and cardiovascular readmissions at 6-month follow-up. These differences were seen despite the fact that the baseline characteristics of patients in the two groups were generally similar. Therefore, eptifibatide provides a clinically effective and economically more attractive alternative to abciximab.