OBJECTIVES: To assess the impact of overweight/obesity on health-related quality of life (HRQL) and health utility in the U.S. METHODS: Adults (age>=18) in the 2000 and 2002 Medical Expenditure Panel Survey (MEPS) were classified as underweight (BMI<18.5), normal weight (BMI:18.5-24.9), overweight (BMI:25-29.9), obese (BMI:30-39.9), and extreme obese (BMI:>=40). HRQL was measured using the SF-12 mental score and physical score. Underweight adults were excluded form the analyses. Health utility was measured using EQ-5D index score and visual analogue scale (EQ-VAS). A stratified matching method was used to compare overweight, obese, and extreme obese samples with the corresponding normal weight samples matched by age, gender, race, current smoking status, and physical activity level. Effect sizes (ES) were estimated. Bonferroni method was used to adjust for multiple comparisons. MEPS individual weights were applied to achieve nationally representative statistics. RESULTS: Of the 36,897 adults in the study sample, 13,521 were with normal weight, 13,631 overweight, 8,435 obese, and 1,310 extremely obese. Descriptive results showed that normal weight sample had the highest average scores in all the HRQL and health utility measures. These findings were further supported by the results using the stratified matching method. Compared to matching normal weight adults, overweight adults had similar SF-12 mental scores and EQ-VAS scores, but significantly lower SF-12 physical scores (ES=6.24, p<0.01) and EQ-5D index (ES=3.72, p<0.01). On average, both obese and extremely obese adults had lower SF-12 mental score (ES=5.25 and 17.23, respectively), SF-12 physical score (ES=23.78 and 60.04, respectively), EQ-5D index (ES=16.92 and 49.99, respectively), and EQ-VAS score (ES=19.17 and 45.33, respectively). All differences were significant at 1%. CONCLUSIONS: Our study showed that obesity is a condition associated with significant reduction of physical and mental HRQL and health utility among adults in the United States. Overweight had a negative impact on physical HRQL and health utility.