Past studies have found that depression is an independent predictor of death in patients after acute myocardial infarction (AMI). Our aim was to investigate whether the adverse effect upon mortality of depression, including mild levels, persisted up to 25 years. We used an historical design to study patients who had been consecutively admitted to hospital after transmural AMI during the 1980s and enrolled in an exercise training trial. The Beck Depression Inventory (BDI) was administered to 188 patients in the third week after hospital admission. Scores were trichotomised and classified as low (0-5), mild (6-9) or moderate to severe (≥10) depression. The Australian National Death Index was used to determine mortality status. Cox proportional-hazards modelling was undertaken to determine the relationship between the trichotomised BDI-I scores and all-cause mortality over five time periods up to 25 years. The mean age of patients was 54.15 years. One hundred fourteen (114) (60.4%) had low or no depression, 47 (25.2%) mild depression and 27 (14.3%) moderate to severe depression. The mortality status of 185 (98.4%) patients was established. Depression was a significant predictor of death, independently of age and severity of myocardial infarction, at 5, 10 and 15 years but not at 20 or 25 years. Patients with mild depression had greater mortality than those with low or moderate to severe depression. Early identification of depression, including milder levels, is important since patients remain at increased risk for many years. They require ongoing monitoring and appropriate treatment.