The aim of the study was to determine the role of obesity evaluated by body mass index (BMI), waist circumference (WC), and their combined effect on all-cause mortality according to age and related risk factors. This study included 119,090 subjects (79,325 men and 39,765 women), aged from 17 years to 85 years, who had a general health checkup at the Centre d’Investigations Préventives et Cliniques, Paris, France. The mean follow-up was 5.6±2.4 years. The prevalence of obesity, defined by WC and BMI categories, was determined according to age groups (<55, 55–65, >65 years). All-cause mortality according to obesity and age was determined using Cox regression analysis, adjusted for related risk factors and previous cardiovascular events. For the entire population, WC adjusted for BMI, an index of central obesity, was strongly associated with mortality, even after adjustment for hypertension, dyslipidemia, and diabetes. The prevalence of obesity increased with age, notably when defined by WC. Nonetheless, the association between WC adjusted for BMI and mortality was not observed in subjects >65 years old (hazard ratio [HR] =1.010, P=NS) but was found in subjects <55 (HR =1.030, P<0.0001) and 55–65 years old (HR =1.023, P<0.05). By contrast, hypertension (HR =1.31, P<0.05), previous cardiovascular events (HR =1.98, P<0.05), and smoking (HR =1.33, P<0.05) remained associated with mortality even after age 65. In conclusion, WC adjusted for BMI is strongly and independently associated with all-cause mortality before 65 years of age, after taking into account the associated risk factors. This relationship disappears in subjects >65 years of age, suggesting a differential impact of visceral fat deposition according to age.