INTRODUCTION: Previous studies have reported a higher prevalence of obesity among rural Americans. However, it is not clear whether obesity-related behaviors can explain the higher level of obesity among rural adults. The purpose of this study was to examine the differences in obesity-related behaviors across rural-urban adult populations in the USA. METHODS: Data were obtained from the 1999-2006 National Health and Nutrition Examination Survey, restricted to 14 039 participants aged 20 years or more. Body mass index (BMI) was calculated using measured height and weight, and individuals with BMI≥30 kg/m2 were categorized as obese. Physical activity recommendations were used to define participants' physical activity levels: no leisure-time physical activity, less than, meeting, and exceeding the recommended levels. Sedentary behaviors were measured by hours sitting and watching TV or videos or using a computer (outside of work). Dietary intake was assessed by one-day 24 hour dietary recall. Residence was measured at the census tract level using the Rural-Urban Commuting Area Codes. Multiple logistic regression models were used to examine urban-rural differences after adjusting for sociodemographic, health, dietary, and lifestyle factors. RESULTS: The prevalence of obesity was higher in rural than in urban residents (35.6% vs 30.4%, p<0.01), among both men (37.7% vs. 32.5%, p<0.01) and women (33.4% vs 28.2%, p<0.01). Compared to urban adults, more rural adults reported no leisure-time physical activity (38.8% vs 31.8%, p<0.01) and fewer rural adults met or exceeded physical activity recommendations (41.5% vs 47.2%, p<0.01). Rural adults had lower intake of fiber and fruits and higher intake of sweetened beverages. After adjusting for sociodemographic, health, diet, sedentary behaviors, and physical activity, the odds of being obese among rural adults were 1.19 times higher than that among urban adults (95% confidence interval: 1.06, 1.34). CONCLUSIONS: Higher level of obesity, physical inactivity, and poor diet among rural residents and the persistent higher risk of obesity among rural adults after adjusting for obesity-related behaviors call for more research into 'obesogenic' environments in rural America. Effective programs are needed to help rural residents reduce high risks for obesity and unhealthy lifestyles.