BACKGROUND: In recent years, significant advances have been made in the pharmaceutical treatment of coronary syndromes. The GPIIb/IIIa receptor antagonists have been shown to increase the success rate of invasive procedures, such as PTCA. However, acquisition costs for these agents are high when compared with traditional therapy (i.e., heparin). Three GPIIb/IIIa receptor antagonists have been approved for use by the US Food and Drug Administration. OBJECTIVE: To assess the relative cost effectiveness of abciximab, eptifibatide, and tirofiban when treating US patients with coronary syndromes. METHODS: A decision analytic model compared the three drugs on the basis of major bleeding events and myocardial infarction. Costs included those for medications and adverse events. Transition probabilities were based on published trials and clinical judgement. The time horizon for the model was 30 days. Cost-effectiveness ratios were computed for the three agents and rank order stability analysis used to test the robustness of results. A hospital perspective was adopted for the analysis. RESULTS: Average per-patient treatment cost was $1,393, $2,480, and $2,409 for eptifibatide, abciximab, and tirofiban, respectively. The probability of successful treatment (i.e., no bleeding or myocardial infarction) was 0.86, 0.89, and 0.78 for eptifibatide, abciximab, and tirofiban, respectively. The cost per successfully treated patient was $1,616, $2,799, and $3,080 for eptifibatide, abciximab, and tirofiban, respectively. The incremental cost of eptifibatide was $45,292 less than abciximab and $12,700 less than tirofiban per successfully treated patient. Estimates of cost effectiveness were robust to alterations in model parameters. In order for eptifibatide and abciximab to be equally cost effective, the bleeding rate for eptifibatide would have to increase by 26.9% or the probability of myocardial infarction for eptifibatide would have to increase by 12.8%. CONCLUSIONS: Results indicate that the higher costs of abciximab and tirofiban may not be justified when treating US patients with coronary syndromes. Our model was limited by the availability of event probability estimates for eptifibatide and tirofiban.