The prevailing view is that women have a higher early mortality after acute myocardial infarction (AMI) than men, but several studies have shown no differences. Further, long-term differences have not been addressed widely. The present study examined gender differences in short- and long-term prognoses after AMI in The Netherlands. A nationwide cohort of 21,565 patients with a first hospitalized AMI in 1995 was identified through linkage of the National Hospital Discharge Register and the population register. Crude short- and long-term mortalities were significantly higher in women than in men (28-day hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.58 to 1.82; 5-year HR 1.52, 95% CI 1.46 to 1.59). After adjustment for age, the risk difference was attenuated at 28 days and even reversed at 5 years in favor of women (28-day HR 1.11, 95% CI 1.03 to 1.20; 5-year HR 0.94, 95% CI 0.90 to 0.99). When differences in other covariates were also taken into account, the risk differences remained virtually the same. To account for differences in reperfusion procedures, we repeated the analyses in 1,176 patients who underwent acute reperfusion therapy (angioplasty/thrombolysis). Comparable, but not statistically significant, gender differences were observed (28-day HR 1.06, 95% CI 0.65 to 1.74; 5-year HR 0.82, 95% CI 0.62 to 1.08). In conclusion, our findings in an unselected cohort covering a complete nation indicate that the worse short- and long-term prognoses after an AMI in women compared with men may largely be explained by differences in age, whereas differences in co-morbidity, origin, infarct location, and reperfusion therapy seem to contribute little.