Context: Women are generally older than men at hospitalization for myocardial infarction (MI) and also present less frequently with chest pain/discomfort. However, few studies have taken age into account when examining sex differences in clinical presentation and mortality. Objective: To examine the relationship between sex and symptom presentation and between sex, symptom presentation, and hospital mortality, before and after accounting for age in patients hospitalized with MI. Design, Setting, and Patients: Observational study from the National Registry of Myocardial Infarction, 1994-2006, of 1 143 513 registry patients (481 581 women and 661 932 men). Main Outcome Measures: We examined predictors of MI presentation without chest pain and the relationship between age, sex, and hospital mortality. Results: The proportion of MI patients who presented without chest pain was significantly higher for women than men (42.0% [95% CI, 41.8%-42.1%] vs 30.7% [95% CI, 30.6%-30.8%]; P<.001). There was a significant interaction between age and sex with chest pain at presentation, with a larger sex difference in younger than older patients, which became attenuated with advancing age. Multivariable adjusted age-specific odds ratios (ORs) for lack of chest pain for women (referent, men) were younger than 45 years, 1.30 (95% CI, 1.23-1.36); 45 to 54 years, 1.26 (95% CI, 1.22- 1.30); 55 to 64 years, 1.24 (95% CI, 1.21-1.27); 65 to 74 years, 1.13 (95% CI, 1.11- 1.15); and 75 years or older, 1.03 (95% CI, 1.02-1.04). Two-way interaction (sex and age) on MI presentation without chest pain was significant (P<.001). The in-hospital mortality rate was 14.6% for women and 10.3% for men. Younger women presenting without chest pain had greater hospital mortality than younger men without chest pain, and these sex differences decreased or even reversed with advancing age, with adjusted OR for age younger than 45 years, 1.18 (95% CI, 1.00-1.39); 45 to 54 years, 1.13 (95% CI, 1.02-1.26); 55 to 64 years, 1.02 (95% CI, 0.96-1.09); 65 to 74 years, 0.91 (95% CI, 0.88-0.95); and 75 years or older, 0.81 (95% CI, 0.79-0.83). The 3-way interaction (sex, age, and chest pain) on mortality was significant (P<.001). Conclusion: In this registry of patients hospitalized with MI, women were more likely than men to present without chest pain and had higher mortality than men within the same age group, but sex differences in clinical presentation without chest pain and in mortality were attenuated with increasing age. ©2012 American Medical Association. All rights reserved.