OBJECTIVES: To test the impact of body mass index (BMI) on health-related quality of life (HRQOL) in overweight and obese individuals. METHODS: Data were obtained from the 2002 Medical Expenditure Panel Survey (MEPS). MEPS collects data on health care use, insurance, access, and satisfaction, along with basic demographic and health status information for a representative sample of the US civilian non-institutionalized population. Our weighted sample consists of 207,969,360 adults. Regression analyses were used to detect independent effects of HRQOL (using EQ-5D US valuation and EQ VAS) on overweight and obese individuals. RESULTS: After adjusting for com-morbidities, smoking status, and socio-demographic variables, respondents with a self-reported BMI >25.0 kg/m^2 reported impaired quality of life. Health-related quality of life diminished with each increasing level of BMI (p<.01). Additionally, HRQOL significantly diminished with increasing age (p<.01). CONCLUSIONS: Our findings suggest a significant impact of BMI on changes in HRQOL that is independent of co-morbidities and socio-demographic variables.