Objectives Our aim was to study the impact of delay from symptom onset to first coronary device on infarct size and clinical outcomes at 30 days and 1 year in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention. Background Longer delay from symptom onset to reperfusion has been linked to increased mortality and worse clinical outcome. The mechanisms underpinning this association are not entirely clear. Methods The INFUSE-AMI trial (INFUSE-Anterior Myocardial Infarction) randomized patients with anterior STEMI undergoing primary percutaneous coronary intervention with bivalirudin anticoagulation within 5 h of symptom onset to intralesion (IL) bolus abciximab versus no abciximab and to thrombus aspiration versus no aspiration. The primary endpoint was contrast magnetic resonance infarct size (IS) (percentage of left ventricular mass) at 30 days. Time to reperfusion was classified as <3 versus ≥3 h. Results There were 280 patients (62%) with <3-h delay and 170 patients (38%) with ≥3-h delay. Patients with longer delay were significantly older, more often women, and diabetic. Earlier reperfusion was not associated with higher rates of final Thrombolysis In Myocardial Infarction flow grade 3 or myocardial blush grade 2/3, but was an independent predictor of smaller IS (p = 0.02 by multivariable linear regression). Mortality at 1 year was reduced in patients with shorter delay to reperfusion (4.0% vs. 9.2%, p = 0.02). Conclusions In patients with large anterior myocardial infarction undergoing relatively early reperfusion, longer delays to reperfusion were associated with larger IS and 1-year mortality, but not with reduced reperfusion success. (The INFUSE - Anterior Myocardial Infarction AMI Study; NCT00976521 )