It is unknown whether the benefits of parenteral platelet glycoprotein (GP) IIb/IIIa inhibitors as an adjunct to percutaneous coronary intervention (PCI) demonstrated in randomized clinical trials extend to patients treated outside the setting of clinical trials. A contemporary registry of 10,847 consecutive PCI procedures was analyzed to determine the effect of GP IIb/IIIa inhibitor treatment on in-hospital major adverse coronary events ([MACEs] composite of death, urgent coronary artery bypass surgery, periprocedural myocardial infarction, abrupt closure, and stent thrombosis). In this registry, GP IIb/IIIa inhibitors were administered to 20.1% of patients. These patients were younger, more often men, and less often hypertensive than untreated patients. GP IIb/IIIa inhibitor-treated patients were more likely to present with acute myocardial infarction or unstable angina. Stents were placed in 79% of patients treated with GP IIb/IIIa inhibitors. MACEs occurred in 7.8% of GP IIb/IIIa inhibitor-treated patients compared with 3.8% of untreated patients (p <0.001). After multivariable adjustment for the propensity of GP IIb/IIIa inhibitor treatment as well as other possible confounders and interactions known to influence MACEs, GP IIb/IIIa inhibitor treatment was associated with a 57% increase in the risk of a MACE (odds ratio 1.57, 95% confidence interval 1.22 to 2.03; p = 0.0004). In a data set consisting of patients with a high degree of acuity predominantly treated with stent placement, GP IIb/IIIa inhibitor treatment is associated with an increase in thrombotic complications of PCI.