Diet is important for the prevention of CVD, and diets high in MUFA might be more cardioprotective than low-fat diets. We hypothesise that inflammation and endothelial cell function will be improved most favourably by a high-MUFA diet compared with a low-fat diet. This was tested in a parallel randomised intervention trial on overweight individuals (aged 28·2 (sd 4·6) years) assigned to a diet moderate in the amount of fat (35–45% of energy; >20% of fat as MUFA; MUFA diet, n 39), a low-fat (20–30% of energy) diet (LF diet, n 43) or a control diet (35 % of energy as fat, n 24) for 6 months after weight loss. Protein constituted 10–20 % of energy in all diets. Food was provided free of charge. Fasting blood samples were collected before and after the intervention and analysed for C-reactive protein (CRP), IL-6, intercellular adhesion molecule, von Willebrand factor (vWF) and tissue factor pathway inhibitor. vWF concentrations tended to fall on the LF diet (4·78 (sd 16·44) %; P = 0·07). Concentrations of IL-6 were reduced by the MUFA (0·37 (sd 0·74) pg/ml; P < 0·01) and LF (0·47 (sd 0·69) pg/ml; P < 0·001) diets, and CRP was reduced on all diets (MUFA: 0·48 (sd 1·93) mg/l (P < 0·01); LF: 1·46 (sd 2·89) mg/l (P < 0·001); control: 1·20 (sd 1·97) mg/l (P < 0·01)). No significant differences were observed between changes induced by the different diets. Our findings suggest that in overweight subjects after weight loss, the MUFA and LF diets have similar long-term effects on inflammation and endothelial cell function.