Because the long-term effects on weight loss and maintenance of a diet with increased protein and reduced carbohydrates are unknown, this study sought to compare changes in body weight and composition and blood lipids after short-term (4 months) weight loss followed by a weight maintenance phase (8 months). After 4 months, individuals on the moderate-protein diet lost 22% more fat mass than those on the conventional high-carbohydrate diet, although weight loss did not differ between the two diets. At 12 months, weight loss still did not differ between the two diets, although the moderate-protein diet generated greater improvements in body composition and more participants completed the study. More participants achieved a weight loss >10% on the moderate-protein diet with a greater decrease in fat mass than subjects on the conventional high-carbohydrate diet. Finally, the moderate-protein diet produced greater reductions in triglycerides and increases in HDL cholesterol than the high-carbohydrate diet.