Background:Obesity is a major public health problem. Detailed knowledge about the relationship between body mass index (BMI) and health-related quality of life (HRQL) is important for deriving effective and cost-effective prevention and weight management strategies. This study aims to describe the sex-, age- and ethnicity-specific association between BMI and HRQL in the US adult population.Methods:Analyses are based on pooled cross-sectional data from 41 459 participants of the Medical Expenditure Panel Survey (MEPS) Household Component (HC) for the years 2000-2003. BMI was calculated using self-reported height and weight, and HRQL was assessed with the EuroQol five-dimensional questionnaire. Generalized additive models were fitted with a smooth function for BMI and a smooth-factor interaction for BMI with sex adjusted for age, ethnicity, poverty, smoking and physical activity. Models were further stratified by age and ethnicity.Results:The association between BMI and HRQL is inverse U-shaped with a HRQL high point at a BMI of 22 kg m '2 in women and a HRQL high plateau at BMI values of 22-30 kg m '2 in men. Men aged 50 years and older with a BMI of 29 kg m '2 reported on average five-point higher visual analog scale (VAS) scores than peers with a BMI of 20 kg m '2. The inverse U-shaped association is more pronounced in older people, and the BMI-HRQL relationship differs between ethnicities. In Hispanics, the BMI associated with the highest HRQL is higher than in white people and, in black women, the BMI-HRQL association has an almost linear negative slope.Conclusions:The results show that a more differentiated use of BMI cutoffs in scientific discussions and daily practice is indicated. The findings should be considered in the design of future weight loss and weight management programs.