Purpose: Osteoporosis affects 4-6 million (13%-18%) postmenopausal white women in the United States. Most studies to date on risk factors for osteoporosis have considered body mass index (BMI) only as a possible confounder. In this study, we assess the direct relationship between BMI and osteoporosis. Methods: We conducted a cross-sectional study among women aged 50-84 years referred by their physicians for a bone mineral density (BMD) examination at Baystate Medical Center between October 1998 and September 2000. BMI was determined prior to the BMD examination in the clinic. Information on other risk factors was obtained through a mailed questionnaire. Ordinal logistic regression was used to model the association between BMI and osteoporosis, controlling for confounding factors. Results: BMI was inversely associated with BMD status. After adjustment for age, prior hormone replacement therapy (HRT) use, and other factors, odds ratios ( OR) for low, high, land obese compared with moderate BMI women were 1.8 (95% CI 1.2-2.7), 0.46 (95% CI 0.29-0.71), and 0.22 (95% CI 0.14-0.36), respectively, with a significant linear trend (p < 0.0001) across BMI categories. Evaluating BMI as a continuous variable, the odds of bone loss decreased 12% for each unit increase in BMI (OR = 0.88, 95% CI 0.85-0.91). Conclusions: Women with low BMI are at increased risk of osteoporosis. The change in risk associated with a 1 unit change in BMI (similar to 5-8 lb) is of greater magnitude than most other modifiable risk factors. To help reduce the risk of osteoporosis, patients should be advised to maintain a normal weight.