The impact of thienopyridine administration prior to primary stenting in acute myocardial infarction (AMI) has not been well studied. We therefore examined the database from the prospective, multicenter, controlled CADILLAC trial in which 1,036 patients were randomized to bare metal stenting with or without abciximab to determine whether patients who received a thienopyridine prior to bare metal stenting in AMI had superior clinical outcomes. Per operator discretion, 659 patients (63.6%; Th+) received either a 500 mg ticlopidine loading dose (n = 623) or a 300 mg clopidogrel loading dose (n = 40), while 377 patients (36.4%; Th-) received no thienopyridine prior to stent implantation. Baseline and procedural characteristics of the two groups, including abciximab use (52.5% vs 52.8%, P = 0.93) were well matched. Th+ compared to Th- patients had lower rates of core lab assessed TIMI 0/1 flow postprocedure (0.8% vs 2.7%, P = 0.01). Th+ compared to Th- patients also had significantly reduced in-hospital and 30-day rates of ischemic target vessel revascularization (TVR) (1.1% vs 3.2%, P = 0.01 and 1.5% vs 3.8%, P = 0.02, respectively) and major adverse cardiovascular events (MACE) (2.7% vs 5.8%, P = 0.01 and 4.0% vs 6.9%, P = 0.03, respectively), results that remained significant after covariate adjustment. In conclusion, in this large prospective, controlled trial, patients receiving a thienopyridine prior to primary stenting in AMI were less likely to have TIMI 0/1 flow postprocedure and experienced reduced in-hospital and 30-day rates of ischemic TVR and MACE compared to those not administered a thienopyridine prior to stent implantation.