- Background Mortality from acute coronary syndrome has historically been higher in women as compared with men. We hypothesized that adoption of a more sensitive definition for the diagnosis of acute myocardial infarction and managing patients according to the 2000 European Society of Cardiology and American College of Cardiology guidelines would reduce this difference. Methods A retrospective cohort study was conducted of all acute coronary syndrome admissions to 7 regional tertiary hospitals in Israel during 1999-2004. The primary end point was all-cause 1-year mortality. Differences in risk between men and women were assessed using Cox proportional hazards regression. Results The number of patients admitted with acute coronary syndrome was 20,206 and 15,583 before and after adoption of the guidelines, respectively. An invasive strategy during the index hospitalization was more frequent in men in both the pre- (47.6% vs 33.6, P <.001) and post- (55.7% vs 40.9%, P <.001) transition periods. Secondary prevention was intensified in the post-transition period in both sexes. Multivariate analysis adjusting for differences in baseline clinical characteristics between men and women and invasive strategy demonstrated that female sex was associated with increased 1-year mortality during the pretransition period (hazard ratio 1.34, 95% confidence interval, 1.24-1.45), but was not a significant factor in the post-transition period (hazard ratio 1.04, 95% confidence interval, 0.94-1.14). Conclusions The transition to the 2000 European Society of Cardiology and American College of Cardiology guidelines was associated with a reduction in the sex-based mortality difference in patients with acute coronary syndrome despite the fact that an early invasive strategy and secondary prevention continued to be underutilized in female patients in both periods.