Minor ST-T abnormalities are common on the resting electrocardiogram of otherwise healthy persons, but the long-term importance of these findings has not been extensively evaluated, especially in women. In a prospective study, 7,985 women and 9,630 men (aged 40 to 64 years at baseline) without other electrocardiographic abnormalities and free of previous coronary heart disease (CHD) were studied using Cox regression for 22-years of follow-up. Primary outcomes were death from CHD and total cardiovascular disease (CVD); total mortality was a secondary outcome. Minnesota Code was employed to assess the presence or absence of electrocardiographic abnormalities. Analyses compared persons with minor Minnesota Code ST-segment (codes 4-3 or 4-4) or T-wave findings (codes 5-3 or 5-4) to those with normal electrocardiographic findings. In combined analyses of men and women adjusted for age, isolated minor T-wave abnormality, minor ST-segment depression, or a combination of minor ST-segment and T-wave abnormalities were each associated with increased mortality risks. For CHD mortality, hazard ratios (HRs) ranged from 1.60 to 2.10; for CVD mortality, HRs ranged from 1.50 to 1.95; and for total mortality, HRs ranged from 1.31 to 1.50 (p <0.05 for all HRs). In separate analyses by gender adjusted for age, increased risks were observed for combined ST-T-wave abnormalities in both genders for CHD and CVD mortality (HR 1.72 to 1.75 for men, p <0.05; HR 2.07 to 2.51 for women, p <0.001). These data indicate that nonspecific (minor) ST-segment depression and/or T-wave abnormalities have a long-term prognostic impact for CHD and CVD death in middle-aged women and men and can be considered markers of heightened CHD and CVD risk.