A high consumption of trans fatty acids increases the risk of cardiovascular disease (CVD). We investigated whether this increase in risk was due to the decrease in serum HDL-cholesterol by trans fatty acids, because low concentrations of serum HDL-cholesterol also increase risk of CVD. Flow-mediated vasodilation (FMD) was used as an endpoint in dietary interventions that were designed to change the concentration of serum HDL-cholesterol within 4 weeks in healthy volunteers. Replacement of 10% of energy from saturated by trans fatty acids decreased serum HDL-cholesterol by 21 % and impaired FMD. However, a replacement of monounsaturated fats by carbohydrates did not impair FMD, although it decreased serum HDL-cholesterol by 13%. Acute postprandial impairments of FMD by either trans fats or saturated fats were not found, suggesting that long-term effects are responsible for the detrimental effect of trans fats on health. However, the role of serum HDL-cholesterol appears to be less than we expected.