Gut-derived hormones affect appetite. Ghrelin increases hunger which decreases after food intake, whereas satiation and satiety are induced by peptide YY (PYY), glucagon-like peptide-1 (GLP-1), and perhaps glucose-dependent insulinotropic polypeptide (GIP) which are increased after food intake [1-3]. These gut-derived appetite hormones have been theorized to play a role in the weight-loss that results from bariatric surgery [4, 5] and agonists of GLP-1 and GIP receptors have become successful medical treatments for obesity [6-8]. Circulating concentrations of gut-derived appetite hormones can be influenced by dietary macronutrient composition [9-13], which provides a theoretical basis for why some diets may help facilitate weight loss better than others. We investigated inpatient adults in a randomized crossover study and demonstrated that, after 2 weeks of eating a low carbohydrate (LC) diet (75.8% fat, 10.0% carbohydrate), a LC meal resulted in significantly greater postprandial GLP-1, GIP, and PYY but lower ghrelin compared to an isocaloric low fat (LF) meal after 2 weeks of eating a LF diet (10.3% fat, 75.2% carbohydrate; all p<0.02). However, the observed differences in gut-derived appetite hormones were incommensurate with subsequent ad libitum energy intake across the day, which was 551±103 kcal (p<0.0001) greater following the LC diet as compared to the LF diet. These data suggest that other diet-related factors can dominate the effects of gut-derived appetite hormones on ad libitum energy intake, at least in the short-term.