Objective: Recently, osteoarthritis (OA) is regarded as another component of metabolic syndrome (MetS). Growing evidence has suggested that metabolic mediators contribute to the initiation and progression of the disease process. Although women suffer drastic metabolic change after menopause, the association between female reproductive factors, metabolic syndrome, sarcopenia and OA is unclear. The purpose of this study was to investigate the association of OA and multiple metabolic factors in midaged women. Methods: This was a cross-sectional study using the fifth Korean National Health and Nutrition Examination Survey (2010-2012) and 3324 women between 50 and 60 years old was included in this study. MetS was diagnosed based on National Cholesterol Education Program-Adult Treatment Panel III criteria, Sarcopenia was defined as lower extremities skeletal muscle mass adjusted by weight. Results: In a multivariable logistic regression analysis, sarcopenia was was associated with radiographic knee OA (odds ratio 1.495;95% confidence interval 0.788-0.859; P=0.03). Even after adjusting for age, BMI, presence of metabolic syndrome, and menopause this association remained significant. Conclusion: There was a significant association between lower extremities skeletal muscle mass and radiographic knee OA in mid-aged women.