The prognostic significance of ST segment depression in patients with their first acute myocardial infarction was investigated in 1444 patients with an acute myocardial infarction, who were randomly assigned to the placebo arm of the Beta-Blocker Heart Attack Trial (BHAT). Patients were divided retrospectively into three groups based on the presence or absence of > or = 1 mm ST segment depression in two contiguous leads of a 12-lead electrocardiogram obtained during the first few days after admission and at the time of randomization, which occurred at 9.7 +/- 3.3 days after the index myocardial infarction. Group 1 included 392 patients with no ST segment depression, group 2 comprised 713 patients with transient ST segment depression in the first few days after admission or at the time of randomization, and group 3 included 339 patients with persistent ST segment depression in the first few days after admission and at the time of randomization. At a median follow-up of 26 months, the mortality rate was 4.9% in group 1, 7.6% in group 2, and 13.6% in group 3. When Cox regression was used to adjust for baseline differences in other variables, the differences between the three groups continued to be highly significant (p = 0.005; 95% confidence intervals [0.6 and 1.4]). We conclude that persistent and transient ST segment depression in patients with their first myocardial infarction are strong predictors of increased long-term mortality when compared to patients without ST segment depression. These findings should be taken into consideration when stratifying patients at risk in the post-myocardial infarction period.