Whether exercise-induced ST-segment depression <1 mm is an independent predictor of future coronary events (CEs) in asymptomatic subjects is unknown. We performed maximal treadmill exercise tests on 1083 volunteers from the Baltimore Longitudinal Study of Aging who were free from clinical coronary heart disease. Exercise ST-segment changes were stratified by Minnesota code criteria: 11:1 (n=213), flat or downsloping ST depression > or =1 mm; 11:2 (n=66), flat or downsloping ST depression > or =0.5 mm and <1 mm; 11:4 (n=124), ST-J depression > or =1 mm with slowly rising ST segments; and 11:5 (n=69), minor ST depression (<0.5 mm) before exercise that worsened to flat or downsloping ST depression > or =1 mm during or after exercise. Risk of CE was compared with subjects with normal exercise ECG (n=611). Over a mean follow-up of 7.9 years, 76 subjects developed CEs (angina pectoris, myocardial infarction, or coronary death). On univariate analysis, age (relative risk [RR]=1.07/year, P<0.0001), male sex (RR=1.98, P=0.009), plasma cholesterol (RR=1.02/mg per dL, P<0.0001), hypertension (RR=2.23, P=0.002), duration of exercise (RR=0.71/min, P=0.0001), and systolic blood pressure at peak effort (RR=1.02/mm Hg, P=0.002) were associated with CE. By Cox proportional hazards analysis, age (RR=1.06/year, P<0.0001), male sex (RR=2.76, P=0.0002), plasma cholesterol (RR=1.02 per 1 mg/dL, P<0.0001), duration of exercise (RR=0.87/min, P=0.004), and ST-segment changes coded as either 11:1 (RR=2.70, P=0.0005) or 11:5 (RR=2.73, P=0.04) were independent predictors of CE. Both a classic ischemic ST-segment exercise response and intensification of minor preexercise ST-segment depression to levels > or =1 mm independently predicted future CE in this asymptomatic population. Neither slowly rising ST depression nor horizontal ST depression <1 mm was prognostic.