Background/Objectives: Observational studies indicate that sugar-sweetened soft drinks (SSSD) may promote obesity, among other factors, owing to low-satiating effects. The effect of energy in drinks on appetite is still unclear. We examined the effect of two isocaloric, but macronutrient, different beverages (SSSD versus semi-skimmed milk) and two non-energy-containing beverages (aspartame-sweetened soft drink (ASSD) and water) on appetite, appetite-regulating hormones and energy intake (EI). Subjects/Methods: In all, 24 obese individuals were included in a crossover trial. Each subject was served either 500 ml of SSSD (regular cola: 900 kJ), semi-skimmed milk (950 kJ), ASSD (diet cola: 7.5 kJ), or water. Subjective appetite scores, ghrelin, GLP-1, and GIP concentrations were measured at baseline and continuously 4-h post intake. Ad libitum EI was measured 4 h after intake of the test drinks. Results: Milk induced greater subjective fullness and less hunger than regular cola (Po0.05). Also, milk led to 31% higher GLP-1 (95% CI: 20, 44; Po0.01) and 45% higher GIP (95% CI: 23, 72; Po0.01) concentrations compared with SSSD. Ghrelin was equally 20% lower after milk and SSSD compared with water. The total EI (ad libitum EI þ EI from the drink) was higher after the energy-containing drinks compared with diet cola and water (Po0.01). Conclusions: Milk increased appetite scores and GLP-1 and GIP responses compared with SSSD. The energy containing beverages were not compensated by decreased EI at the following meal, emphasizing the risk of generating a positive energy balance by consuming energy containing beverages. Furthermore, there were no indications of ASSD increased appetite or EI compared with water.