Purpose: The purpose of this study was to estimate the differences in prevalence of metabolic syndrome and its individual components across rural-urban populations, as well as to determine the risk factors associated with metabolic syndrome and examine how they contribute toward rural-urban disparity.Methods: Data came from the 1999-2006 National Health and Nutrition Examination Survey, restricting to 6,896 participants aged 20 years or more with complete information. Metabolic syndrome was defined using the National Cholesterol Education Program's Adult Treatment Panel III criteria. Residence was measured at the census tract level using the Rural-Urban Commuting Area Codes. We estimated the prevalence of metabolic syndrome and its components by residence. Multiple logistic regression models were used to examine urban-rural differences after adjusting for sociodemographic, health, dietary, and lifestyle factors.Results: The prevalence of metabolic syndrome was higher in rural than urban residents (39.9% vs 32.8%), among both men (39.7% vs 33.3%) and women (40.2% vs 32.3%, respectively). The age and sex adjusted OR for metabolic syndrome in rural as compared to urban residents was 1.23 (95% CI, 1.02-1.49), which was attenuated to 1.06 (95% CI, 0.90-1.25) after adjusting for covariates. Older age, lower physical activity, higher screen time, higher meat intake, and skipping breakfast were associated with increased odds of metabolic syndrome.Conclusion: Rural dwelling was associated with higher prevalence of metabolic syndrome among adults in the Unites States, which can be attributed to the differences in demographic composition and obesity-related behavioral factors between urban and rural residents.