BackgroundEvidence that high-protein diets are an effective strategy for the maintenance of long-term weight loss is limited. ObjectiveThe objective was to determine the efficacy of a higher protein intake on the maintenance of weight loss after 64 wk of follow-up. DesignSeventy-nine healthy women with a mean (±SD) age of 49 ± 9 y and a body mass index (in kg/m2) of 32.8 ± 3.5 completed an intensive 12-wk weight-loss program and 52 wk of follow-up to compare the effects on weight-loss maintenance of a high-protein (HP) diet (34% of energy) or a high-carbohydrate (HC) diet (64% of energy). ResultsMean (±SD) weight loss was not significantly different between groups: (HP: 4.6 ± 5.5 kg; HC: 4.4 ± 6.1 kg). Protein intake (g) from dietary records at 64 wk was directly related to weight loss (P < 0.0001), accounting for 15% of the variance. Protein intake as a percentage of energy was also related to weight change (P = 0.003), accounting for 10% of the variance. In the upper tertile (88 g protein/d), weight loss was 6.5 ± 7.5 and 3.4 ± 4.4 kg (P = 0.03) in the 2 lower tertiles, respectively. This difference did not translate to a difference in central fat loss between groups. Lipids, glucose, insulin, C-reactive protein, and homocysteine all improved with weight loss and were not significantly different between groups. HDL cholesterol rose by 20%. Higher serum vitamin B-12 was observed in the HP group, and folate concentrations were not significantly different between groups. ConclusionsA reported higher protein intake appears to confer some weight-loss benefit. Cardiovascular disease risk factors, biomarkers of disease, and serum vitamins and minerals improved with no differences between groups.