This study provides findings to assist in identifying factors that contribute to the current clinical and public health debate of the obesity epidemic. The study examined the genetics of adult-onset weight change in middle-aged male—male twins controlling for weight in early adulthood, lifetime history of tobacco use and alcohol dependence, and aimed to estimate the proportion of genetic factors that influence weight change between early adulthood and middle age in white middle-class males. The study was a classic longitudinal twin design and used Body Mass Index (BMI) for three waves of data collection from the Vietnam Era Twin Registry — induction physicals (∼ 1968), 1987 and 1990 — or periods corresponding between young adulthood and middle age. Univariate heritability estimates for BMI at all three data periods were conducted as well as a Cholesky longitudinal genetic analysis for weight change controlling for BMI at military induction, smoking and alcohol use. Frequency data indicated that the sample was on average classified as normal BMI in their 20s; but BMI gradually increased during the next twenty years. Univariate data for each data period indicated that additive genetic factors accounted for between 63% and 69% of total variance in BMI. The Cholesky longitudinal genetic analysis of BMI87 and BMI90, controlling for BMI at military induction, indicated that more than half of the change in BMI from early adulthood to middle age remains heritable. No shared environmental factors were identified, thus the remainder of the variance was accounted for by nonshared, or unique, environmental factors and error. The data analysis suggests that treatments and public health interventions need to recognize the magnitude of genetic factors if short-term and long-term interventions are to be effective.