Background: People worldwide are becoming obese at earlier ages, increasing exposure to long-term obesity. Purpose: To examine how BMI at age 25 years predicts later obesity and test the importance of long-term obesity beyond obesity severity for adult cardiovascular, inflammatory, and metabolic risk. Methods: Data from adults aged 35-64 years from the 1999-2010 U.S. National Health and Nutrition Examination Survey were analyzed in 2013 to test how BMI at age 25 years predicts later adult BMI. Next, logistic regression models predicted the odds of elevated risk for blood pressure (BP); high-density lipoprotein cholesterol; total cholesterol; triglycerides; C-reactive protein (CRP); and glycosylated hemoglobin (HbA1c) by BMI at age 25 years and current BMI. Results: Men obese at age 25 years had a 23.1% estimated probability, of Class III obesity after age 35 years, compared to a 1.1% probability for men of normal weight at this age. For women, these probabilities were 46.9% and 4.8%, respectively. Those obese in both periods had higher odds of elevated BP, CRP, and HbA1c compared to those of normal weight at age 25 years, with no effects for lipids. After adjustment for current BMI, these associations were either eliminated (for BP and CRP) or greatly reduced (HbA1c). Conclusions: The biological risks of long-term obesity are primarily due to the risk of more severe obesity later in life among those obese early in life, rather than obesity duration. Current body weight rather than duration may be the best reflection of clinical cardiovascular and metabolic risk. (C) 2014 American Journal of Preventive Medicine