Diabetes mellitus is strongly associated with increased cardiovascular morbidity and mortality in patients with ST-segment elevation myocardial infarction. It is unknown whether myocardial perfusion is decreased in diabetic compared with nondiabetic patients after primary percutaneous coronary intervention (PCI), which may contribute to their worse prognosis. We compared myocardial perfusion and infarct sizes between diabetic and nondiabetic patients undergoing PCI for acute ST-segment elevation myocardial infarction in the EMERALD trial. EMERALD was a prospective, randomized, multicenter study evaluating distal embolic protection during primary PCI in ST-segment elevation myocardial infarction. End points included final myocardial blush grade, complete ST-segment resolution (STR) 30 minutes after PCI, and final infarct size as determined by technetium-99m single proton emission computed tomography measured between days 5 and 14. Of 501 patients, 62 (12%) had diabetes mellitus. Diabetic patients had impaired myocardial perfusion after PCI as measured by myocardial blush grade 0/1 (34% vs 16%, p = 0.002) and lower rates of complete 30-minute STR (45% vs 65%, p = 0.005). Infarct size (median 20% vs 11%, p = 0.005), development of new onset severe congestive heart failure (12% vs 4%, p = 0.016), and 30-day mortality (10% vs 1%, p <0.0001) were also greater in diabetic patients. After multivariate adjustment, diabetes remained associated with lack of complete STR and mortality at 6 months. Use of distal protection devices did not improve outcomes in diabetic or nondiabetic patients. In conclusion, in patients with ST-segment elevation myocardial infarction undergoing primary PCI, diabetes is independently associated with decreased myocardial reperfusion, larger infarct, development of congestive heart failure, and decreased survival.