Background and aimsThe relationship between dietary macronutrient composition and appetite is controversial. We examined the effects of a year-long low-carbohydrate diet compared to a low-fat diet on appetite-related hormones and self-reported change in appetite. Methods and resultsA total of 148 adults with a body mass index 30–45 kg/m2, who were free of diabetes, cardiovascular disease and chronic kidney disease at baseline were randomly assigned to either a low-carbohydrate diet (carbohydrate [excluding dietary fiber]<40 g/day; N = 75) or a low-fat diet (<30% energy from fat, <7% from saturated fat; N = 73). Participants in both groups attended individual and group dietary counseling sessions where they were provided the same behavioral curriculum and advised to maintain baseline levels of physical activity. Appetite and appetite-related hormones were measured at 0, 3, 6 and 12 months of intervention. At 12 months, mean changes (95% CI) in peptide YY were −34.8 pg/mL (−41.0 to −28.6) and in the low-carbohydrate group and −44.2 pg/mL (−50.4 to −38.0) in the low-fat group (net change: 9.54 pg/mL [0.6 to 18.2]; p = 0.036). Approximately 99% of dietary effects on peptide YY are explained by differences in dietary macronutrient content. There was no difference in change in ghrelin or self-reported change in appetite between the groups. ConclusionsA low-fat diet reduced peptide YY more than a low-carbohydrate diet. These findings suggest that satiety may be better preserved on a low-carbohydrate diet, as compared to a low fat diet.Trial Registration: clinicaltrials.gov Identifier: NCT00609271.