We investigated whether ultra-processed foods affect energy intake in 20 weight-stable adults, aged (mean ± SE) 31.2 ± 1.6 years and BMI = 27 ± 1.5 kg/m2. Subjects were admitted to the NIH Clinical Center and randomized to receive either ultra-processed or unprocessed diets for 2 weeks immediately followed by the alternate diet for 2 weeks. Meals were designed to be matched for presented calories, energy density, macronutrients, sugar, sodium, and fiber. Subjects were instructed to consume as much or as little as desired. Energy intake was greater during the ultra-processed diet (508 ± 106 kcal/day; p = 0.0001), with increased consumption of carbohydrate (280 ± 54 kcal/day; p < 0.0001) and fat (230 ± 53 kcal/day; p = 0.0004), but not protein (−2 ± 12 kcal/day; p = 0.85). Weight changes were highly correlated with energy intake (r = 0.8, p < 0.0001), with participants gaining 0.9 ± 0.3 kg (p = 0.009) during the ultra-processed diet and losing 0.9 ± 0.3 kg (p = 0.007) during the unprocessed diet. Limiting consumption of ultra-processed foods may be an effective strategy for obesity prevention and treatment. Display omitted •20 inpatient adults received ultra-processed and unprocessed diets for 14 days each•Diets were matched for presented calories, sugar, fat, fiber, and macronutrients•Ad libitum intake was ∼500 kcal/day more on the ultra-processed versus unprocessed diet•Body weight changes were highly correlated with diet differences in energy intake Hall et al. investigated 20 inpatient adults who were exposed to ultra-processed versus unprocessed diets for 14 days each, in random order. The ultra-processed diet caused increased ad libitum energy intake and weight gain despite being matched to the unprocessed diet for presented calories, sugar, fat, sodium, fiber, and macronutrients.