BACKGROUND: The role of sex differences in health-related quality of life (HRQoL) after myocardial infarction (MI) remains controversial. METHODS: In total 408 Norwegian patients completed the Short Form 36 (SF-36) questionnaire 2.5 years after MI. We compared HRQoL between sexes and with national norms. Multiple linear regression analysis was used to explore the association of scores on the Physical (PCS) and Mental (MCS) component summary scales with clinical and sociodemographic variables. RESULTS: Women scored lower than norms on the Physical functioning, Role functioning-physical, General health, and Role functioning-emotional scales. Men scored higher on Bodily pain, and lower on the other 7 scales compared to norms. Women <70 years scored lower than men on 3 out of 8 scales and on PCS. Women >/=70 scored lower than men on 5 out of 8 scales and on PCS. Relative to sex- and age-specific norms, there were no sex-differences in SF-36 scores. Age, time since the index MI, chronic obstructive pulmonary disease (COPD), previous MI, and stroke predicted PCS scores in women. Education, COPD, infarct localization, number of indications for cardiovascular medication at discharge, medication for heart failure, and subsequent MI predicted PCS scores in men. Smoking status, education, and Q-wave MI were determinants for MCS scores in men. CONCLUSION: Patients had impaired HRQoL compared to sex- and age-specific norms 2.5 years after MI. Women had lower HRQoL scores than men, but relative to norms HRQoL was equally affected in both sexes. Men and women had different determinants of HRQoL.