The role of obesity and overweight as independent risk factors for cardiovascular disease is still debated. The aim of this study was to evaluate the impact of overweight on cardiovascular mortality according to the presence or absence of associated risk factors. This study included 139,562 men and 104,236 women, aged 18 to 95 years, who had a standard health checkup at the IPC Center between 1972 and 1988. The follow-up period for mortality ended in December 1997. In both genders, the prevalence of hypertension, diabetes, and hypercholesterolemia increased with body mass index (P<0.001). When compared with subjects with a body mass index <25 kg/m2 without associated risk factors, overweight subjects without associated risk factors did not have an increased risk of cardiovascular mortality. Risk of cardiovascular death increased significantly when overweight was associated with hypertension alone [hazard ratio: 2.05 (1.71 to 2.46) in men; 2.15 (1.48 to 3.11) in women]. In both genders, the association of overweight with diabetes alone or hypercholesterolemia alone did not increase the risk. By contrast, in the presence of hypertension, cardiovascular mortality dramatically increased in overweight subjects with hypercholesterolemia [hazard ratio: 2.65 (2.20 to 3.19) in men, 2.57 (1.80 to 3.68) in women] or diabetes [hazard ratio: 3.01 (2.29 to 3.95) in men; 4.50 (2.67 to 7.58) in women]. The data suggest that the presence of high blood pressure in overweight subjects is the key factor leading to a significant increase in cardiovascular mortality. Because overweight significantly increases the prevalence of associated risk factors, especially hypertension, it should be considered as a major cardiovascular risk determinant.