OBJECTIVES: We sought to compare outcomes in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) with or without previous coronary artery bypass grafts (CABG). BACKGROUND: Limited information exists regarding procedural success and clinical outcomes of STEMI patients with CABG undergoing primary PCI. METHODS: The APEX-AMI (Assessment of Pexelizumab in Acute Myocardial Infarction) trial was a randomized, placebo-controlled trial of pexelizumab in STEMI patients with planned primary PCI: 128 of 5,745 (2.2%) patients had prior CABG. Clinical/procedural characteristics, culprit vessel (infarct-related artery [IRA]), and 90-day clinical outcomes were compared. RESULTS: Patients with previous CABG were more frequently men, older, had a higher incidence of comorbidities and multivessel disease. In patients with versus without prior CABG, PCI was performed less frequently, that is, 78.9% versus 93.9%; of those with prior CABG receiving PCI, Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 was also restored less often, that is, 82.5% versus 91.6% (both p < 0.001). In prior CABG, there was a nearly even designation of the IRA as a bypass graft (n = 63) versus a native vessel (n = 55): IRA post-PCI TIMI flow grade 3 was achieved in 66.7% versus 88.0%, respectively (p = 0.043). Prior CABG patients had increased 90-day death and composite 90-day death/congestive heart failure/shock. Excess death remained significant after multivariable adjustment (hazard ratio: 1.9, 95% confidence interval: 1.08 to 3.33, p = 0.025). When prior CABG patients were stratified by the type of IRA, there was further discrimination of the increased 90-day death, that is, 19% bypass graft (n = 63) versus 5.7% native vessel (n = 55, p = 0.05), respectively. CONCLUSIONS: Prior CABG patients with STEMI are less likely to undergo acute reperfusion, have worse angiographic outcomes following primary PCI, and higher 90-day mortality. These findings are especially applicable when the IRA was a bypass graft.