Diet is important in the prevention of cardiovascular disease, and it has been suggested that a high-MUFA diet is more cardioprotective than a low-fat diet. We hypothesised that the postprandial thrombotic risk profile is improved most favourably by a high-MUFA diet compared with a low-fat diet. This was tested in a parallel intervention trial on overweight individuals (aged 28.4 (SD 4.7) years) randomly assigned to a MUFA-diet (35-45% of energy as fat; >20% as MUFA, n=21) or a low-fat (LF) diet (20-30% of energy as fat, n=22) for 6months after a weight loss of ~10%. All foods were provided free of charge from a purpose-built supermarket. Meal tests designed after the same principles were performed before and after the dietary intervention, and blood samples were collected at 8.00h (fasting), 12.00h, and 18.00h and analysed for factor VII coagulant activity (FVII:C), activated FVII, fibrinogen, prothrombin fragment 1+2 (F1+2), D-dimer, plasminogen activator inhibitor (PAI:Ag), and thrombin activatable fibrinolysis inhibitor. There were significant postprandial increases in F1+2 and D-dimer before and after dietary intervention, with significantly lower values after 6months. No significant differences were observed between the postprandial changes induced by the two diets. The postprandial decrease in FVII:C and PAI:Ag did not differ before and after intervention, irrespective of the diets. Our findings suggest postprandial coagulation activation in overweight subjects with more pronounced acute than long-term effects. We observed similar effects of the MUFA diet and the LF diet on the postprandial prothrombotic risk profile.