Current literature provides limited information about healthy volunteers serving as controls for biomedical research. This study describes trends in body mass index (BMI), a ratio of weight to height (kg/m2), of the population of healthy volunteers at the National Institutes of Health Clinical Center (NIH CC) and compares these trends to a nationally-representative sample as reported by the National Health and Nutrition Examination Survey (NHANES). We hypothesized that BMI trends at the NIH CC would follow those of the US population. This cross-sectional study examined the BMI of healthy volunteers at the NIH CC from 1976-80, 1981-87, 1988-94, 1995-98, and for all subsequent two-year periods onward until 2012. Study data were extracted from the NIH Biomedical Translational Research Information System (BTRIS). Subjects were selected based on a discharge code of “volunteer.” Descriptive statistics of volunteers at the NIH CC were calculated for height, weight, age-adjusted BMI, age, and gender, and associations between categorical variables were analyzed using the χ2-test. Differences between BMI categories or time periods for continuous independent variables were assessed using Kruskal-Wallis and post-hoc Tamhane T2 tests. The 13,898 healthy volunteers with median age of age 34 years were 53% female and primarily non-Hispanic whites. Mean BMI was within the normal category from 1976-1987. From 1988 on, mean BMI fluctuated, but increased overall. The BMI of healthy volunteers at the NIH CC appears to follow national trends as described by NHANES data of increasing body weight during the past three decades followed by a recent plateau.