The importance of systemic/metabolic factors in the association of obesity with radiographic knee osteoarthritis (OA) was examined for 3,905 adults aged 45 to 74 from the United States National Health and Nutrition Examination Survey, 1971 to 1975 (NHANES I). Obesity was associated with both bilateral and unilateral OA, but more strongly with bilateral OA. Obesity was also associated with both symptomatic and nonsymptomatic knee OA. Controlling for age, sex, serum cholesterol, serum uric acid, diabetes, body fat distribution, bone density, and blood pressure did not significantly reduce the association between obesity and knee OA. Findings from these data are not supportive of a metabolic link between obesity and knee OA.