BACKGROUND: The acute benefits of platelet glycoprotein IIb/IIIa inhibitors for non-ST-segment elevation acute coronary syndromes (NSTE ACS) remain unclear. METHODS: In this pilot trial, 311 patients with NSTE ACS were randomly assigned in the emergency department to double-blinded therapy with eptifibatide or placebo for 12 to 24 hours before crossover to open-label eptifibatide. Serial creatine-kinase MB (CK-MB) and quantitative cardiac troponin T levels were collected during the first 24 hours to assess the impact of early platelet glycoprotein IIb/IIIa blockade on infarct size as measured by cardiac markers. RESULTS: Median peak CK-MB (10.3 vs 11.8 ng/mL; P =.71) and peak quantitative cardiac troponin T levels (0.2 vs 0.3 ng/mL; P =.95) were similar between treatment groups, respectively. Median calculated peak CK-MB values (41 vs 40 ng/mL; P =.72) and area under the CK-MB curve measurements (980 vs 764 microg/min/L; P =.68) from curve-fitting analyses that could be performed in 106 of 311 patients were also similar. CONCLUSIONS: In this pilot trial, early administration of eptifibatide in the emergency department did not modulate serologic measurements of infarct size in patients with NSTE ACS.