OBJECTIVE: Results on the association between vitamin D and blood pressure are conflicting and little is known about how their relationship may be affected by obesity. Thus, we explored whether waist circumference modified the association between serum 25-hydroxyvitamin D (25(OH)D) and blood pressure in participants of the U.S. National Health and Nutrition Examination Surveys 2001-2006. METHODS: We included 10 331 nonpregnant participants aged 20 years or older. The association of serum 25(OH)D with systolic and diastolic blood pressure, in the total sample and stratified by waist circumference category (abdominal overweight: 80 to <88 cm in females / 94 to <102 cm in males; abdominal obesity: ≥88 cm in females/ ≥102 cm in males), was examined using multiple linear regression. Effect modification by waist circumference was assessed through a cross-product interaction term between 25(OH)D category and waist circumference category. RESULTS: Waist circumference significantly modified the inverse association between 25(OH)D and systolic blood pressure (SBP) (P value for interaction: 0.09). A stronger association of 25(OH)D levels below 15 ng/ml (reference: ≥30 ng/ml) with SBP was found in abdominally obese (β = 3.5 mmHg) than in abdominally overweight (β = 2.0 mmHg) and normal waist participants (β = 1.2 mmHg), but this interaction was only significant in participants without antihypertensive treatment. No significant effect modification was found for diastolic blood pressure. CONCLUSION: Results from this large, cross-sectional sample suggest that the association between 25(OH)D and SBP is stronger in individuals with abdominal obesity than in those with a normal waist or with abdominal overweight.