Conflicting results have been reported on the possible existence of sex differences in mortality after myocardial infarction (MI). There is also a scarcity of data on the impact of sex on outcomes after ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI). The aim of this study was to analyze sex difference trends in sex-related differences in mortality for STEMI and NSTEMI. A retrospective analysis of 445 145 episodes of MI (2005-2015) was carried out using information from the Spanish National Health System. The incidence rates were expressed as events per 10 000 person-years. The denominators (age-specific groups) were obtained from the nationwide census. We calculated crude and adjusted (multilevel logistic regression) mortality. Poisson regression analysis was used to study temporal trends for in-hospital mortality. A total of 69.8% episodes occurred in men. The mean age in men was 66.1±13.3 years, which was significantly younger than in women, 74.9±12.1 (P<.001). A total of 272 407 (61.2%) episodes were STEMI, and 172 738 (38.8%) were NSTEMI. Women accounted for 28.8% of STEMI and 33.9% of NSTEMI episodes (P <.001). The effect of female sex on risk-adjusted models for in-hospital mortality was the opposite in STEMI (OR for women, 1.18; 95%CI, 1.14-1.22; P <.001) and NSTEMI (OR for women, 0.85; 95%CI, 0.81-0.89; P <.001). MI hospitalization rates were higher in men than in women for all age groups [20 vs 7.7 per 10 000 individuals aged 35-94 years (P <.001)], with a trend to diminish in both sexes. Women had a slight but significantly increased risk of in-hospital mortality after MI, but the effect of sex depended on MI type, with women exhibiting higher mortality for STEMI and lower mortality for NSTEMI. Copyright © 2020. Published by Elsevier España, S.L.U.