Activation of platelets is central to the pathophysiology of unstable angina. We studied whether inhibition of the final common pathway for platelet aggregation with tirofiban, a nonpeptide glycoprotein IIb/IIIa receptor antagonist, would improve clinical outcome in this condition. In a double-blind study, we randomly assigned 3232 patients who were already receiving aspirin to additional treatment with intravenous tirofiban for 48 hours. The primary end point was a composite of death, myocardial infarction, or refractory ischemia at 48 hours. The incidence of the composite end point was 32 percent lower at 48 hours in the group that received tirofiban (3.8 percent, vs. 5.6 percent with heparin; risk ratio, 0.67; 95 percent confidence interval, 0.48 to 0.92; P=0.01). Percutaneous revascularization was performed in 1.9 percent of the patients during the first 48 hours. At 30 days, the frequency of the composite end point (with the addition of readmission for unstable angina) was similar in the two groups (15.9 percent in the tirofiban group vs. 17.1 percent in the heparin group, P=0.34). There was a trend toward a reduction in the rate of death or myocardial infarction with tirofiban (a rate of 5.8 percent, as compared with 7.1 percent in the heparin group; risk ratio, 0.80; 95 percent confidence interval, 0.61 to 1.05; P=0.11), and mortality was 2.3 percent, as compared with 3.6 percent in the heparin group (P=0.02). Major bleeding occurred in 0.4 percent of the patients in both groups. Reversible thrombocytopenia occurred more frequently with tirofiban than with heparin (1.1 percent vs. 0.4 percent, P=0.04). Tirofiban was generally well tolerated and, as compared with heparin, reduced ischemic events during the 48-hour infusion period, during which revascularization procedures were not performed. The incidence of refractory ischemia and myocardial infarction was not reduced at 30 days, but mortality was lower among the patients given tirofiban. Platelet inhibition with aspirin plus tirofiban may have a role in the management of unstable angina.