BACKGROUND It is not clear whether varying the protein-to-carbohydrate ratio of weight-loss diets benefits body composition or metabolism. OBJECTIVE The objective was to compare the effects of 2 weight-loss diets differing in protein-to-carbohydrate ratio on body composition, glucose and lipid metabolism, and markers of bone turnover. METHODS A parallel design included either a high-protein diet of meat, poultry, and dairy foods (HP diet: 27% of energy as protein, 44% as carbohydrate, and 29% as fat) or a standard-protein diet low in those foods (SP diet: 16% of energy as protein, 57% as carbohydrate, and 27% as fat) during 12 wk of energy restriction (6-6.3 MJ/d) and 4 wk of energy balance ( approximately 8.2 MJ/d). Fifty-seven overweight volunteers with fasting insulin concentrations > 12 mU/L completed the study. RESULTS Weight loss (7.9 +/- 0.5 kg) and total fat loss (6.9 +/- 0.4 kg) did not differ between diet groups. In women, total lean mass was significantly (P = 0.02) better preserved with the HP diet (-0.1 +/- 0.3 kg) than with the SP diet (-1.5 +/- 0.3 kg). Those fed the HP diet had significantly (P < 0.03) less glycemic response at weeks 0 and 16 than did those fed the SP diet. After weight loss, the glycemic response decreased significantly (P < 0.05) more in the HP diet group. The reduction in serum triacylglycerol concentrations was significantly (P < 0.05) greater in the HP diet group (23%) than in the SP diet group (10%). Markers of bone turnover, calcium excretion, and systolic blood pressure were unchanged. CONCLUSIONS Replacing carbohydrate with protein from meat, poultry, and dairy foods has beneficial metabolic effects and no adverse effects on markers of bone turnover or calcium excretion.