We tested whether trans fatty acids and saturated fatty acids had different effects on flow-mediated vasodilation (FMD), a risk marker of coronary heart disease (CHD). Consumption of trans fatty acids is related to increased risk of CHD, probably through effects on lipoproteins. Trans fatty acids differ from most saturated fatty acids because they decrease serum high-density lipoprotein (HDL) cholesterol, and this may increase the risk of CHD. We fed 29 volunteers 2 controlled diets in a 2x4-week randomized crossover design. The "Trans-diet" contained 9.2 energy percent of trans fatty acids; these were replaced by saturated fatty acids in the "Sat-diet." Mean serum HDL cholesterol after the Trans-diet was 0.39 mmol/L (14.8 mg/dL), or 21% lower than after the Sat-diet (95% CI 0.28 to 0.50 mmol/L). Serum low density lipoprotein and triglyceride concentrations were stable. FMD+SD was 4.4+/-2.3% after the Trans-diet and 6.2+/-3.0% after the Sat-diet (difference -1.8%, 95% CI -3.2 to -0.4). Replacement of dietary saturated fatty acids by trans fatty acids impaired FMD of the brachial artery, which suggests increased risk of CHD. Further studies are needed to test whether the decrease in serum HDL cholesterol caused the impairment of FMD.