Our aim was to determine whether short-term weight loss on a low-carbohydrate/low-saturated fat diet improved endothelial function compared with a conventional high-carbohydrate diet, as this diet is expected to lower both blood glucose and LDL-cholesterol. In a randomised parallel design of two energy-restricted diets in an outpatient setting, thirty-six subjects (BMI 33 (sem 4) kg/m2) were randomised to a low- or high-carbohydrate diet both low in saturated fat. Flow-mediated dilatation (FMD), fasting glucose, insulin, lipids, adiponectin and adhesion molecules were measured at baseline, during weight loss and at 52 weeks. FMD did not change with either diet (5.2 (sem 0.6) to 5.5 (sem 0.6) %) despite weight loss of 5 % and significant reductions in glucose and insulin and LDL-cholesterol and was not different after sustained weight loss of 5 % at 52 weeks. Adiponectin fell by 6 % at 12 weeks (P = 0.1) with weight loss but rose by 17 % at 12 months (P < 0.05) with 5 % weight loss. There were no effects of diet. In contradistinction, adhesion molecules fell at 12 weeks, vascular cell adhesion molecule-1 by 14 % and intracellular adhesion molecule-1 by 13 % (both P < 0.05). There were correlations between change in adiponectin at 12 months and change in HDL (r 0.778, P < 0.01) and glucose (r - 0.563, P = 0.057). In summary, weight loss does not improve FMD. Novel cardiovascular risk factors improved at 12 weeks but the improvement in adiponectin was delayed.