Purpose: Relationships between body weight and disease are not straightforward. Central obesity appears to be a relatively greater cardiovascular risk factor than generalized obesity. The purpose of this study was to evaluate body mass index (BMI) and waist circumference and the association of obesity distribution with blood estrogen levels (estradiol, bioavailable estradiol, and estrone). Methods: The study cohort consisted of 207 postmenopausal women enrolled in the Women's Ischemia Syndrome Evaluation (WISE) undergoing angiography for evaluation of suspected ischemia. Results: Both BMI and waist circumference were positively associated with all three blood estrogen levels (p < 0.01), with the highest estrogen levels found in the obese women with large waists (p < 0.01). Results from regression analyses confirmed significant associations of BMI and waist circumference with the estrogen levels. Conclusions: These results demonstrate differing relationships between blood estrogen levels and obesity distribution in a cohort of postmenopausal women with chest pain undergoing coronary angiography. The differing levels by general and central obesity may help explain in part observed epidemiological relationships between obesity and disease. © Mary Ann Liebert, Inc.