Our objective was to examine whether elevated α-lactalbumin (αlac) protein intake compared to elevated supra sustained milk protein (SSP) and sustained milk protein (SP) intake results into a difference in body weight and body composition over a 6-month energy-restriction intervention. Body weight, body composition, resting energy expenditure (REE), satiety and blood- and urine-parameters of 87 subjects (BMI 31 ± 5 kg/m(2) and fat percentage 40 ± 8%) were assessed before and after daily energy intakes of 100, 33, and 67% for 1, 1, and 2 months respectively (periods 1, 2, and 3), with protein intake from meal replacements and 2 months of 67% with ad libitum protein intake additional to the meal replacements (period 4). The diets resulted in 0.8 ± 0.3 g/kg body mass (BM) for SP and significant higher protein intake (24-h nitrogen) of 1.2 ± 0.3 and 1.0 ± 0.3 g/kgBM for SSP and αlac (P < 0.05). Body weight and fat percentage was decreased in all groups after 6 months (SP -7 ± 5 kg and -5 ± 3%; SSP -6 ± 3 kg and -5 ± 3%; αlac -6 ± 4 kg and -4 ± 4%, P < 0.001; there was no significant group by time difference). Furthermore, sparing of fat-free mass (FFM) and preservation of REE in function of FFM during weight loss was not significantly different between the αlac-group and the SSP- and SP-groups. In conclusion, the efficacy of αlac in reduction of body weight and fat mass (FM), and preservation of FFM does not differ from the efficacy of similar daily intakes of milk protein during 6 months of energy restriction.