Abstract Background It has been shown that, among patients with ST-segment elevation myocardial infarction (STEMI), diabetes is associated with a significantly higher mortality. The aim of this study was to investigate in a large cohort of patients the impact of diabetes on mortality in a large cohort of patients with STEMI treated with primary angioplasty. Methods Our population is represented by consecutive patients with STEMI treated by primary angioplasty and enrolled in the POLISH registry in 2003. All clinical, angiographic, and follow-up data were prospectively collected. Diagnosis of diabetes was based on history of diabetes at admission. Results Among 7193 patients, 877 (12.2%) had diabetes at admission. Diabetes was associated with more advanced age (p<0.0001), higher prevalence of female gender (p<0.0001), hyperlipidemia (p<0.0001), shock at presentation (p<0.0001), renal failure (p<0.0001), previous myocardial infarction (p<0.0001), more often treated after 6h from symptom onset (p<0.0001). Diabetes was associated with more extensive coronary artery disease (p<0.0001), less often treated with stenting (p<0.0001). Diabetes was significantly associated with impaired epicardial reperfusion (TIMI 0–2: OR [95% CI]=1.81 [1.5–2.18], p<0.0001), that persisted after correction for baseline confounding factors (OR [95% CI]=1.33 [1.075–1.64], p=0.009). At a mean follow-up of 524±194 days, diabetes was associated with higher mortality (unadjusted cumulative mortality: 23.5% vs. 12.6%, unadjusted HR=1.95 [1.66–2.3], p<0.0001), that persisted after correction for confounding factors (adjusted cumulative mortality: 13.3% vs. 10.7%, adjusted HR=1.23 [1.04–1.46], p=0.013). Conclusions This study shows that among STEMI treated by primary angioplasty diabetes is independently associated with impaired epicardial reperfusion and higher mortality.