Previous studies have demonstrated a significant interaction between gender and age after medically treated acute myocardial infarction (AMI), when younger women were found to have a higher mortality rate than younger men, but the mortality rate for older men and women was similar. The study objective was to determine whether a gender–age interaction exists for AMI treated exclusively with primary angioplasty. This analysis was a retrospective cohort study of 9,015 consecutive patients who underwent primary angioplasty for AMI in New York State from 1997 to 1999. The primary end point of interest was in-hospital mortality. A logistic regression model was constructed to determine the relation between gender and mortality among patients with AMI treated with angioplasty. Additional analyses were performed to test whether a mortality difference existed according to age. In-hospital mortality rate was twofold higher in women than in men (6.7% vs 3.4%, p <0.001). After adjusting for age, co-morbid conditions, and hemodynamic status by multivariable logistic regression analysis, the odds ratio for in-hospital death for women was no longer significant (odds ratio 1.21, 95% confidence interval 0.69 to 2.10, p = 0.51). Among patients <75 years of age, women had a 37% increased risk of in-hospital mortality (adjusted odds ratio 1.37, 95% confidence interval 1.01 to 1.98, p = 0.04), whereas there was no significant difference in mortality between men and women who were ≥75 years of age. In conclusion, female gender was found to be an independent predictor of in-hospital mortality in patients <75 years of age after primary angioplasty for AMI.