The objective of this analysis was to assess risk factors for self-reported osteoarthritis (OA) in an ethnically diverse cohort of women. The participants were postmenopausal women aged 50 to 79 (n=146,494) participating in the clinical trial and observational study of the Women's Health Initiative (WHI). Baseline OA and risk factors were collected from WHI questionnaires. Logistic regression was used to find the association between the risk factors and OA. Risk factor distribution and ethnicity interaction terms were used to assess ethnic differences in OA risk. Forty-four percent of the participants reported OA. Older age (odds ratio (OR)(70-79 vs 50-59)=2.69, 95% confidence interval (CI)=2.60-2.78) and higher body mass index (BMI) (OR(BMI>or=40.0 vs <24.9)=2.80, 95% CI=2.63-2.99) were found to be the strongest risk factors associated with self-reported OA. The prevalence of obesity (BMI>or=30.0) was 57.9% in African Americans, 51.0% in American Indians, 41.9% in Hispanic whites, and 32.9% in non-Hispanic whites. The prevalence of other major OA risk factors was higher in African-American, American-Indian, and Hispanic white women than in non-Hispanic white women. Non-Hispanic white women who were in the extreme obese category (BMI>or=40.0 kg/m(2)) had a 2.80 times (95% CI=2.63, 2.99) greater odds of self-reported OA. The odds were even higher in American-Indian (OR=4.22, 95% CI=1.82, 9.77) and African-American (OR=3.31, 95% CI=2.79, 3.91) women, indicating a significant interactive effect of BMI and ethnicity on odds of OA. In conclusion, OA is a highly prevalent condition in postmenopausal women, and there are differential effects according to ethnicity.