IntroductionMuch of the data on BMI-mortality associations stem from 20thcentury U.S. cohorts. The purpose of this study was to determine the association between BMI and mortality in a contemporary, nationally representative, 21stcentury, U.S. adult population.MethodsThis was a retrospective cohort study of U.S. adults from the 1999–2018 National Health Interview Study (NHIS), linked to the National Death Index (NDI) through December 31st, 2019. BMI was calculated using self-reported height & weight and categorized into 9 groups. We estimated risk of all-cause mortality using multivariable Cox proportional hazards regression, adjusting for covariates, accounting for the survey design, and performing subgroup analyses to reduce analytic bias.ResultsThe study sample included 554,332 adults (mean age 46 years [SD 15], 50% female, 69% non-Hispanic White). Over a median follow-up of 9 years (IQR 5–14) and maximum follow-up of 20 years, there were 75,807 deaths. The risk of all-cause mortality was similar across a wide range of BMI categories: compared to BMI of 22.5–24.9 kg/m2, the adjusted HR was 0.95 [95% CI 0.92, 0.98] for BMI of 25.0–27.4 and 0.93 [0.90, 0.96] for BMI of 27.5–29.9. These results persisted after restriction to healthy never-smokers and exclusion of subjects who died within the first two years of follow-up. A 21–108% increased mortality risk was seen for BMI ≥30. Older adults showed no significant increase in mortality between BMI of 22.5 and 34.9, while in younger adults this lack of increase was limited to the BMI range of 22.5 to 27.4.ConclusionThe risk of all-cause mortality was elevated by 21–108% among participants with BMI ≥30. BMI may not necessarily increase mortality independently of other risk factors in adults, especially older adults, with overweight BMI. Further studies incorporating weight history, body composition, and morbidity outcomes are needed to fully characterize BMI-mortality associations.