BACKGROUND: Gender differences in management and outcomes have been reported in acute coronary syndrome (ACS). OBJECTIVES: To assess such gender differences in a Swiss national registry. METHODS: 20 290 patients with ACS enrolled in the AMIS Plus Registry from January 1997 to March 2006 by 68 hospitals were included in a prospective observational study. Data on patients' characteristics, diagnoses, procedures, complications and outcomes were recorded. Odds ratios (ORs) of in-hospital mortality were calculated using logistic regression models. RESULTS: 5633 (28%) patients were female and 14 657 (72%) male. Female patients were older than men (mean (SD) age 70.9 (12.1) vs 63.4 (12.9) years; p<0.001), had more comorbidities and came to hospital later. They underwent percutaneous coronary intervention (PCI) less frequently (OR = 0.65; 95% CI 0.61 to 0.69) and their unadjusted in-hospital mortality was higher overall (10.7% vs 6.3%; p<0.001) and in those who underwent PCI (3.0% vs 4.2%; p = 0.018). Mortality differences between women and men disappeared after adjustments for other predictors (adjusted OR (aOR) for women vs men: 1.09; 95% CI 0.95 to 1.25), except in women aged 51-60 years (aOR = 1.78; 95% CI 1.04 to 3.04). However, even after adjustments, female gender remained significantly associated with a lower probability of undergoing PCI (OR = 0.70; 95% CI 0.64 to 0.76). CONCLUSIONS: The analysis showed gender differences in baseline characteristics and in the rate of PCI in patients admitted for ACS in Swiss hospitals between 1997 and 2006. Reasons for the significant underuse of PCI in women, and a slightly higher in-hospital mortality in the 51-60 year age group, need to be investigated further.