Aims Controversy exists regarding the early use of glycoprotein IIb/IIIa inhibitors (GPIs) in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). The Assessment of Pexelizumab in Acute Myocardial Infarction (APEX-AMI) trial provides a unique opportunity to examine early vs. late or non-use of GPIs in a large STEMI cohort treated with PCI.Methods and resultsIn the APEX-AMI trial, 3969 of 5707 patients received one of three GPIs at the operator's discretion (abciximab, eptifibatide, tirofiban). Of GPI-treated patients, the median time from symptom onset to GPI administration was 180 min (25th, 75th percentile: 130, 258); 1125 received the agent prior to arriving in the catheterization laboratory [pre-sheath; GPI to sheath insertion: 37 min (16, 66)], whereas 2844 patients were treated after arrival in the catheterization laboratory [in-lab; sheath insertion to GPI: 16 min (10, 27)]. The pre-sheath use of GPIs was associated with a significantly lower hazard of 90-day mortality [adjusted hazard ratio (HR) 0.68, 95 confidence interval (CI) 0.48-0.95, P = 0.025] and of 90-day composite of death/CHF/shock (adjusted HR 0.81, 95 CI 0.65-1.00, P = 0.054). In-hospital severe and moderate bleeding was not related to the use of GPIs. Conclusion This retrospective analysis from a large patient cohort with acute STEMI undergoing PCI suggests that pharmacological pre-treatment of PCI with GPIs, particularly abciximab, was associated with significantly lower occurrence of 90-day clinical outcomes and supports the pre-procedural administration of GPIs in this clinical setting.Clinical trial registration information: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00091637.