Hypoenergetic very low-carbohydrate and low-fat diets are both commonly used for short-term weight loss; however, few studies have directly compared their effect on blood lipids, with no studies to our knowledge comparing postprandial lipemia, an important independently identified cardiovascular risk factor. The primary purpose of this study was to compare the effects of a very low-carbohydrate and a low-fat diet on fasting blood lipids and postprandial lipemia in overweight men. In a balanced, randomized, crossover design, overweight men (n = 15; body fat >25%; BMI, 34 kg/m(2)) consumed 2 experimental diets for 2 consecutive 6-wk periods. One was a very low-carbohydrate (<10% energy as carbohydrate) diet and the other a low-fat (<30% energy as fat) diet. Blood was drawn from fasting subjects on separate days and an oral fat tolerance test was performed at baseline, after the very low-carbohydrate diet period, and after the low-fat diet period. Both diets had the same effect on serum total cholesterol, serum insulin, and homeostasis model analysis-insulin resistance (HOMA-IR). Neither diet affected serum HDL cholesterol (HDL-C) or oxidized LDL (oxLDL) concentrations. Serum LDL cholesterol (LDL-C) was reduced (P < 0.05) only by the low-fat diet (-18%). Fasting serum triacylglycerol (TAG), the TAG/HDL-C ratio, and glucose were significantly reduced only by the very low-carbohydrate diet (-44, -42, and -6%, respectively). Postprandial lipemia was significantly reduced when the men consumed both diets compared with baseline, but the reduction was significantly greater after intake of the very low-carbohydrate diet. Mean and peak LDL particle size increased only after the very low-carbohydrate diet. The short-term hypoenergetic low-fat diet was more effective at lowering serum LDL-C, but the very low-carbohydrate diet was more effective at improving characteristics of the metabolic syndrome as shown by a decrease in fasting serum TAG, the TAG/HDL-C ratio, postprandial lipemia, serum glucose, an increase in LDL particle size, and also greater weight loss (P < 0.05).