Chronic insulin resistance contributes to subclinical inflammation, thrombosis/impaired fibrinolysis, and dyslipidemia. The effect of dietary carbohydrate, specifically of glycemic index (GI) and glycemic load (GL), on established and emerging coronary heart disease risk factors has not been elucidated fully. We conducted a randomized crossover feeding study of matched diets differing only in GI and GL in 24 overweight or obese but otherwise healthy men to investigate the effects on insulin sensitivity, inflammation, thrombosis/fibrinolysis, lipoproteins/lipids, and body composition. All meals for the high- and low-GI/GL diets were prepared in a metabolic kitchen. Each participant consumed both diets in random order for 4 weeks each, with a 4-week washout period in between. Each participant underwent a frequently sampled intravenous glucose tolerance test for assessment of insulin sensitivity; blood sampling for the measurement of inflammatory markers, coagulation factors, and lipoproteins/lipids; and dual-energy x-ray absorptiometry for assessment of body composition at the beginning and end of each dietary period. There were no statistically significant differences in glucose metabolism factors, inflammatory markers, or coagulation factors after 4 weeks on the high- and low-GI/GL diets. The high-GI/GL diet resulted in a slightly greater reduction in fat mass and a slightly greater increase in lean mass compared with the low-GI/GL diet. The high-GI/GL diet resulted in significant, but unexpected, reductions in total and low-density lipoprotein cholesterol, whereas high-density lipoprotein cholesterol concentration was significantly reduced on the high-GI/GL diet compared with the low-GI/GL diet. Overall, high- and low-GI/GL diets of 4 weeks' duration had no consistent effects on coronary heart disease risk factors in this group of overweight/obese men. © 2009 Elsevier Inc. All rights reserved.