The purpose of the present study was, first, to detect possible changes in health-related quality of life (HRQL) over time and, second, to predict HRQL at 1 year based on measures made 1 week and 5 months after a first-time acute myocardial infarction. There was an improvement in HRQL at 1 year, as measured by the questionnaire 36-item Medical Outcomes Study Short-Form (SF-36), for both men and women as compared with the assessment 5 months after the acute myocardial infarction. However, the pattern was somewhat different for women and men. Women mainly reported increased scores on scales reflecting better mental health, whereas men, on the whole, demonstrated higher scores in the physical health domain. Depression (HAD) and fatigue were identified as early predictors of lower HRQL at the 1-year follow-up. Our conclusion is that early assessment of fatigue and depression is worthwhile, as they may indicate decreased HRQL in men and women 1 year after first-time myocardial infarction.