OBJECTIVES: This study analyzed lifetime health and economic consequences of multiple obesity-related diseases (ORDs), including diabetes, hypertension, coronary heart disease (CHD), and stroke. METHODS: Nationally representative data of the U.S. civilian, non-institutionalized population was used. Our sample was from the National Health Interview Survey (NHIS), 1997-2000, and linked to the NHIS Linked Mortality Public-Use Files to estimate mortality risks. The sample was further linked to the Medical Expenditure Panel Survey (MEPS) to estimate annual healthcare expenditures. Disease risks were estimated with National Health and Nutrition Examination Survey (NHANES) data. Analyses were stratified by gender and adjusted for age, race, and BMI groups. Complex sampling designs in NHIS, MEPS, and NHANES were adjusted for. A Markov model populated by estimates of disease and mortality risks and healthcare expenditures was built to compute life years and lifetime healthcare expenditures for gender-race-age-BMI-specific subpopulations. RESULTS: Our sample comprised of 17,917 women and 13,928 men. For individuals age 40, life years lost associated with ORDs for women ranged from 2.7 (obese, not white or black, with CHD) to 14.6 (normal-weight, white, with all four ORDs) and for men from 2.3 (obese, not white or black, with diabetes) to 12.4 (normal-weight, not white or black, with all four ORDs). Lifetime healthcare expenditure increment associated with ORDs for women ranged from $27,749 (normal-weight, white, with hypertension) to $277,949 (overweight, not white or black, with all four ORDs) and for men from $41,804 (normal-weight, black, with hypertension) to $249,829 (overweight, not white or black, with all four ORDs). CONCLUSIONS: This study suggests that the lifetime health and economic consequences associated with ORDs are higher for women than men. And disease burden increases with increasing number of ORDs. Diabetes is the most costly ORD. Among sets of two ORDs, the combination of diabetes and hypertension is the most costly.