Although various risk factors have been implicated in the progression of coronary artery disease (CAD), coronary risk factors specifically related to the long-term prognosis for high-risk CAD have not been determined. The study enrolled 311 consecutive Japanese patients with CAD who underwent diagnostic coronary arteriography and divided them into 2 groups: (i) 135 high-risk patients with either impaired left ventricular function (ejection fraction<50%) or multivessel disease and (ii) 176 low-risk patients with normal left ventricular function and 0-or 1-vessel disease. The prevalence of risk factors including age, gender, smoking, hypertension, diabetes mellitus (DM), obesity and lipid variables were compared between the 2 groups. The prevalence of DM, a serum high-density lipoprotein (HDL)-cholesterol level below 35mg/dl and a serum lipoprotein (Lp) (a) level above 25mg/dl was significantly higher in the high-risk group as compared with the low-risk group. Multiple logistic regression analysis demonstrated that DM (odds ratio (OR): 1.72, 95% confidence intervals (CI): 1.02-2.92, p<0.05), a low HDL-cholesterol level (OR: 2.49, 95% CI: 1.49-4.17, p<0.001) and a high Lp(a) level (OR: 1.68, 95% CI: 1, 02-2.76, p<0.05) were all independent risk factors for high-risk CAD. However, if the patients with 0-vessel disease were excluded from the low-risk group, a low HDL-cholesterol level was found to be the only independent predictor for high-risk CAD (OR: 2.07, 95% CI: 1.15-3.70, p<0.05). Among both men and smokers in this population, a higher Lp(a) level was found to be a significant predictor for high-risk CAD. A low serum level of HDL-cholesterol, a high serum level of Lp(a) and DM were significant predictors of high-risk in patients with CAD. Among patients with a significant coronary stenosis or left ventricular dysfunction, a low serum level of HDL-cholesterol was the only significant predictor for high-risk CAD.