BACKGROUND: Altering the macronutrient composition of the diet influences hunger and satiety. Studies have compared high- and low-protein diets, but there are few data on carbohydrate content and ketosis on motivation to eat and ad libitum intake. OBJECTIVE: We aimed to compare the hunger, appetite, and weight-loss responses to a high-protein, low-carbohydrate [(LC) ketogenic] and those to a high-protein, medium-carbohydrate [(MC) nonketogenic] diet in obese men feeding ad libitum. DESIGN: Seventeen obese men were studied in a residential trial; food was provided daily. Subjects were offered 2 high-protein (30% of energy) ad libitum diets, each for a 4-wk period-an LC (4% carbohydrate) ketogenic diet and an MC (35% carbohydrate) diet-randomized in a crossover design. Body weight was measured daily, and ketosis was monitored by analysis of plasma and urine samples. Hunger was assessed by using a computerized visual analogue system. RESULTS: Ad libitum energy intakes were lower with the LC diet than with the MC diet [P=0.02; SE of the difference (SED): 0.27] at 7.25 and 7.95 MJ/d, respectively. Over the 4-wk period, hunger was significantly lower (P=0.014; SED: 1.76) and weight loss was significantly greater (P=0.006; SED: 0.62) with the LC diet (6.34 kg) than with the MC diet (4.35 kg). The LC diet induced ketosis with mean 3-hydroxybutyrate concentrations of 1.52 mmol/L in plasma (P=0.036 from baseline; SED: 0.62) and 2.99 mmol/L in urine (P<0.001 from baseline; SED: 0.36). CONCLUSION: In the short term, high-protein, low-carbohydrate ketogenic diets reduce hunger and lower food intake significantly more than do high-protein, medium-carbohydrate nonketogenic diets.