BACKGROUND: A high triglyceride (TG)--low high-density lipoprotein cholesterol (HDL-C) level (TG > or =1.60 mmol/L [> or =142 mg/dL] and HDL-C < or =1.18 mmol/L [< or =46 mg/dL]) is associated with a high risk of ischemic heart disease (IHD), whereas a low TG--high HDL-C level (TG < or =1.09 [< or =97 mg/dL] and HDL-C > or =1.48 mmol/L [> or =57 mg/dL]) is associated with a low risk. Conventional risk factors tend to coexist with high TG--low HDL-C levels. We tested the hypothesis that subjects with conventional risk factors would still have a low risk of IHD if they had low TG--high HDL-C levels. METHODS: Observational cohort study of 2906 men aged 53 to 74 years free of IHD at baseline. RESULTS: During 8 years, 229 subjects developed IHD. Stratified by conventional risk factors-low-density lipoprotein cholesterol level (< or =4.40 mmol/L or >4.40 mmol/L [< or =170 mg/dL or >170 mg/dL] [median value]), hypertensive status (blood pressure >150/100 mm Hg or taking medication), level of physical activity (>4 h/wk or < or =4 h/wk), and smoking status (nonsmokers vs smokers)-the incidence in men with high TG--low HDL-C levels was 9.8% to 12.2% in the low-risk and 12.2% to 16.4% in the high-risk strata; the corresponding values in men with low TG--high HDL-C concentrations were 4.0% to 5.1% and 3.7% to 5.3%, respectively. Based on an estimate of attributable risk, 35% of IHD might have been prevented if all subjects had had low TG--high HDL-C levels. CONCLUSION: Men with conventional risk factors for IHD have a low risk of IHD if they have low TG--high HDL-C levels.