ST-segment elevation acute myocardial infarction (AMI) in patients who have undergone previous coronary artery bypass grafting (CABG) is associated with low reperfusion rates and poor outcome after fibrinolytic therapy. The efficacy of a combination strategy (reduced fibrinolytic plus platelet glycoprotein IIb/IIIa agent) in this setting is unknown. In the Global Use of Streptokinase and TPA for Occluded coronary arteries V (GUSTO V) trial, 553 patients with a history of CABG were treated with standard-dose reteplase (n = 273), or half-dose reteplase and full-dose abciximab (n = 280) in the first 6 hours of evolving ST-segment elevation MI. Mortality at 30 days was significantly higher in patients who underwent prior CABG compared with patients with no prior CABG (odds ratio [OR] 1.64, 95% confidence interval [CI] 1.21 to 2.24, p = 0.001). In patients who underwent prior CABG, mortality at 7 days was reduced 15% with combination therapy compared with reteplase alone, which was not statistically significant (OR 0.85, 95% CI 0.40 to 1.81, p = 0.66). Patients who underwent prior CABG treated with the combination therapy had fewer episodes of recurrent ischemia (OR 0.60, 95% CI 0.37 to 0.96, p = 0.02), high degree atrioventricular block (OR 0.17, 95% CI 0.02 to 0.82, p = 0.01), and ventricular tachycardia (OR 0.29, 95% CI 0.07 to 0.96, p = 0.04). There was a trend toward reduced urgent revascularization (OR 0.61, 95% CI 0.36 to 1.03, p = 0.06) but no significant difference in reinfarction (OR 0.61, 95% CI 0.31 to 1.52, p = 0.40). In the GUSTO V trial, patients who underwent prior CABG had significantly higher event rates compared with patients without CABG. As in the overall trial, combination therapy in patients who underwent prior CABG led to a consistent reduction in key secondary complications of AMI, including recurrent ischemia and a trend toward reduced urgent revascularization.