Background: The prevalence of obesity in the United States has increased dramatically. Objective: The aim of this study was to determine trends in carbohydrate, fat, and protein intakes in adults and their association with energy intake by using data from the National Health and Nutrition Examination Survey (NHANES) - a representative sample of the US population. Design: Data on adults aged 20-74 y from the first NHANES (NHANES I, 1971-1975; n = 13,106) were compared with data from NHANES 2005-2006 (n = 4381). Normal weight was defined as a body mass index (BMI; in kg/m2) of 19 to <25, overweight as a BMI of 25 to <30, and obese as a BMI of ≥30. Carbohydrate, fat, and protein intakes were obtained by dietary recall. Regression analyses were adjusted for potential confounders. Results: The prevalence of obesity increased from 11.9% to 33.4% in men and from 16.6% to 36.5% in women. The percentage of energy from carbohydrates increased from 44.0% to 48.7%, the percentage of energy from fat decreased from 36.6% to 33.7%, and the percentage of energy from protein decreased from 16.5% to 15.7%. Trends were identical across normal-weight, overweight, and obese groups. Energy intake increased substantially in all 3 BMI groups. In NHANES 2005-2006, a 1% increase in the percentage of energy from protein was associated with a decrease in energy intake of 32 kcal (substituted for carbohydrates) or 51 kcal (substituted for fat). Similar findings were seen across all BMI categories, in men and women, and in NHANES I. Conclusions: Energy intake and the prevalence of obesity have increased dramatically. Dietary interventions should focus on decreasing energy intake and potentially by substituting protein for fat or carbohydrates. © 2011 American Society for Nutrition.