OBJECTIVES: The aim of this study was to determine correlates of acute/subacute coronary stent thrombosis among unselected patients treated in the era of routine dual antiplatelet therapy and specifically to investigate the influence of prophylactic administration of glycoprotein IIb/IIIa (GpIIb-IIIa) inhibitors and use of clopidogrel versus ticlopidine on the development of coronary stent thrombosis (ST). BACKGROUND: Because of a relative infrequency of ST events and relatively uniform practice patterns within randomized trials, previous studies have had a limited ability to address whether the use of different antiplatelet regimens at the time of coronary stenting is associated with differences in ST. METHODS: We performed a multicenter, case-control study to evaluate clinical, angiographic, and pharmacologic/procedural correlates of ST. Between 1996 and 2000, all cases of angiographically-confirmed ST (n = 145) among patients receiving dual antiplatelet therapy were identified from 10 participating clinical sites and were matched with a control without ST randomly selected from the same institution. RESULTS: Multivariable conditional logistic regression identified higher pre-procedure platelet count, stenting for acute myocardial infarction, use of a coil or self-expanding stent, and overt angiographic thrombus prior to the procedure, as independent predictors of ST (all P < .05). After adjusting for these factors, the use of clopidogrel (vs ticlopidine) was independently associated with an increased risk of ST (OR 2.1, 95% CI 1.0-4.1, P = .04). The use of prophylactic glycoprotein IIb/IIIa inhibitors was not associated with reduced ST in the overall analysis, but appeared to confer some protection against ST within the first 24 hours post procedure (OR 0.5 [95% CI 0.2-1.1] for ST during first day, OR 1.7 [95% CI 0.7-4.3] for ST on subsequent days). CONCLUSION: Both biologic and pharmacologic factors are independently associated with acute/subacute ST. The association between clopidogrel use (vs ticlopidine) and increased ST in this analysis requires confirmation in adequately powered clinical trials and suggests a potential role for newer and more potent antiplatelet agents.