Body mass index (BMI) and waist circumference are independently associated with blood pressure, but the dependence of these associations on gender and age has not been clarified. We investigated the associations of BMI and waist circumference with systolic (SBP) and diastolic (DBP) blood pressure and assessed possible interactions with gender and age. Data concerning blood pressure and anthropometric variables were collected at enrollment in a cohort study from 10,928 non-smoking adults, all over Greece, who have never received antihypertensive treatment. Multiple regression-derived standardized coefficients were estimated to compare effects among variables. Among men, waist circumference appears more important than BMI in the prediction of SBP (standardized coefficients 2.26 vs. 1.52 mmHg/SD), and to a lesser extent DBP. In contrast, among women, BMI is more important than waist circumference, in the prediction of SBP (standardized coefficients 3.97 vs. 1.56 mmHg/ SD) and to a lesser extent DBP. The different effects of BMI and waist circumference on blood pressure by gender are evident among older individuals (> 55 years); among younger individuals BMI and waist circumference have comparable effects in both genders. Among younger individuals, BMI and waist circumference are independent and equally important predictors of SBP and DBP in both genders, whereas among older individuals waist circumference is the dominant predictor of blood pressure among men and BMI is the dominant predictor of blood pressure among women. Associations are more evident with respect to SBP than DBP.