BACKGROUND: Mortality rates in females who survived acute myocardial infarction (AMI) exceed those in males. Differences between sexes in age, cardiovascular risk factors and revascularization therapy have been proposed as possible reasons. OBJECTIVE: To select sets of female and male patients comparable in respect of relevant risk factors in order to compare the sex-specific risk in a systematic manner. METHODS: Data of the ISAR-RISK and ART studies were investigated. Patients were enrolled between 1996 and 2005 and suffered from AMI within 4 weeks prior to enrolment. Patients of each sex were selected with 1:1 equivalent age, previous AMI history, sinus-rhythm presence, hypertension, diabetes mellitus, smoking status, left ventricular ejection fraction (LVEF), and revascularization therapy. Survival times were compared between sex groups in the whole study cohort and in the matched cohort. RESULTS: Of 3840 consecutive AMI survivors, 994 (25.9%) were females and 2846 (74.1%) were males. Females were older and suffered more frequently from hypertension and diabetes mellitus. In the whole cohort, females showed an increased mortality with a hazard ratio (HR) of 1.54 compared to males (p<0.0001). The matched cohort comprised 802 patients of each sex and revealed a trend towards poorer survival in females (HR for female sex 1.14; p = 0.359). However, significant mortality differences with a higher risk in matched females was observed during the first year after AMI (HR = 1.61; p = 0.045) but not during the subsequent years. CONCLUSION: Matched sub-groups of post-AMI patients showed a comparable long-term mortality. However, a female excess mortality remained during first year after AMI and cannot be explained by differences in age, cardiovascular risk factors, and modes of acute treatment. Other causal factors, including clinical as well as psychological and social aspects, need to be considered. Female post-AMI patients should be followed more actively particularly during the first year after AMI.