A high protein intake (approximately 40% of energy intake) combined with aerobic and resistance exercise training is more closely associated with improved body composition and cardiovascular risk profile than a traditional protein intake (approximately 15% of intake) combined with moderate-intensity aerobic exercise. However, there is concern that such high-protein diets may adversely affect health. We therefore tested the hypothesis that moderate protein intake (approximately 25% of energy intake) would elicit similar benefits on body composition and metabolic profile as high protein intake. Twenty-four overweight/obese men and women (body mass index [BMI] = 32.2 +/- 3.4, percentage of body fat [%BF] = 37.3 +/- 8.0) were matched for BMI and %BF and randomly assigned to one of 3 groups for a 3-month nutrition/exercise training intervention: (1) high-protein diet (approximately 40% of energy intake) and combined high-intensity resistance and cardiovascular training (HPEx, n = 8, 5 female and 3 male), (2) moderate-protein diet (approximately 25% of energy intake) and combined high-intensity resistance and cardiovascular training (MPEx, n = 8, 5 female and 3 male), or (3) high-protein diet only (HPNx, n = 8, 5 female and 3 male). Total and regional body composition (dual-energy x-ray absorptiometry), insulin sensitivity (insulin sensitivity index to the oral glucose tolerance test), insulin-like growth factor-1 (IGF-1), IGF binding protein-1 (IGFBP-1), IGF binding protein-3 (IGFBP-3), and blood lipids were measured at baseline and after the intervention. All groups experienced significant (P < .05) and similar losses of body weight, BMI, and total and abdominal %BF, and similar improvements in insulin sensitivity (HPEx, 6.3 +/- 1.2 vs 9.5 +/- 0.98; MPEx, 6.2 +/- 1.4 vs 8.4 +/- 1.6; HPNx, 3.7 +/- 1.1 vs 7.0 +/- 1.1; insulin sensitivity index to the oral glucose tolerance test; P < .05) and leptin levels. Furthermore, the HPEx group demonstrated decreases in total cholesterol (TC) and triglycerides, and increases in IGF-1 and IGFBP-1. The MPEx group experienced decreases in TC, whereas the HPNx group had increases in high-density lipoprotein cholesterol, TC to high-density lipoprotein, IGF-1, and IGFBP-1. In conclusion, moderate protein intake elicits similar benefits in body composition and insulin sensitivity as a high-protein diet. These findings may have practical implications for individuals interested in diets containing elevated dietary protein.