In diabetic population cardiovascular morbidity is high and the effects of genetic predisposition remain elucidated. In a large-scale multicenter-based diabetic population, clinical parameters including conventional cardiovascular risk factors and first-degree family history (FH) of diabetes, hypertension, coronary heart disease (CHD) and stroke were investigated in association with presence of CHD and stroke. Among 3611 diabetic patients, 181 (5.0%) had CHD and 118 (3.3%) had stroke. After adjustment for conventional risk factors, FH of CHD (OR 2.32, p<0.0001) and of diabetes (OR 1.44, p<0.05) were associated with CHD, and FH of stroke (OR 1.86, p<0.01) was associated with stroke. FH of hypertension was significantly associated with presence of hypertension and obesity. Synergistic effect of FH of CHD in combination with hypertension or aging on increasing CHD, and that of FH of stroke in combination with microalbuminuria on increasing stroke were found. FH of diabetes, of hypertension, of CHD and of stroke were significantly associated with FH of each disease, indicating clustering of FH. In diabetic population, FH of CHD and FH of stroke doubled the risk of CHD and stroke, respectively, and had synergistic effect in combination with other risk factors. Clustering of FH may indicate interrelation of genetic predisposition.