Background Risk factors for cerebral infarction have not been well clarified, except for hypertension (HT), and few studies have examined the risk factors in the elderly. Methods and Results Clinical and behavioral risk factors for cerebral infarction were examined in 4,349 Japanese men aged 45-74 years with a serum total cholesterol (TC) concentration of 220 mg/dl or greater who participated in the Kyushu Lipid Intervention Study. A total of 81 men developed definite cerebral infarction in a 5-year follow-up period. The Cox proportional hazards model was used with serum TC at baseline and during the follow-up, serum high-density lipoprotein-cholesterol (HDL-C), HT, diabetes mellitus (DM), and other factors as covariates. Serum TC during the follow-up, not at baseline, was positively associated with cerebral infarction, showing a stronger association in the elderly (≥65 years old) than in the middle-aged (<65 years old). Statin use was related to a moderate decrease in the risk of cerebral infarction when follow-up TC was not considered, but the decrease was almost nullified after adjustment for follow-up TC. A low concentration of serum HDL-C, diabetes mellitus, hypertension, and angina pectoris were each related to an increased risk. No clear association was observed for body mass index, smoking or alcohol use. Conclusions Lowering cholesterol is important in the prevention of cerebral infarction in men with moderate hypercholesterolemia. A low concentration of HDL-C, DM, and HT are independent predictors of cerebral infarction. (Circ J 2005; 69: 1 - 6)