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Objectives To assess sex differences in clinical presentation, in-hospital and long-term outcome in ST-elevated myocardial infarction (STEMI) patients undergoing primary PCI (PPCI). Background Several studies have shown higher rates of mortality in women. These differences are not always confirmed after adjusting for confounding variables. Methods From January 2007 to December 2011, 325 consecutive patients (23.1% females and 76.9% males) were prospectively treated and retrospectively analyzed. Primary outcome was in-hospital and long-term mortality. Results Women were older (71.8 ± 11.7 vs. 62.5 ± 12.6 years; p < 0.0001), presented more renal failure (45.3% vs. 20.8%; p < 0.0001) and severe haemodynamic impairment (9.3% vs. 3.6%; p = 0.04). In-hospital overall mortality (14.7% vs. 4.8%; p = 0.003) and cardiac death (12% vs. 2%; p = 0.002) were significantly higher in women. The multivariate analysis identified age (OR 1.07; 95% CI: 1.01–1.13), resuscitated cardiac arrest (CCA) and cardiogenic shock (CS) (OR 15.31; 95% CI: 4.30–61.75), renal failure (OR 0.20; 95% CI: 0.06–0.68), but not sex (OR 1.49; 95% CI: 0.53–4.22) as independent prognostic factors of in-hospital mortality. During a median follow-up of 46.5 months (IQR range 32.7–63.1 months), long-term overall mortality (24.2% vs. 11.0%; p = 0.007) and cardiac death (4.8% vs. 1.7%; p = 0.02) were significantly higher in women. The multivariate analysis identified age (HR 1.06; 95% CI: 1.02–1.11), previous AMI (HR 3.9; 95% CI: 1.63–9.35), renal failure (HR 5.21; 95% CI: 2.12–12.85), technical success (HR 0.35; 95% CI: 0.14–0.84) but not sex (HR 0.90; 95% CI: 0.42–1.94) as independent prognostic factors of long-term mortality. Conclusions Worse clinical presentation rather than sex may explain the excess of mortality in women with STEMI undergoing PPCI. [ABSTRACT FROM AUTHOR]