Cholesteryl ester transfer protein (CETP) may promote reverse cholesterol transport. An elevated concentration of high-density lipoprotein cholesterol (HDL-C) is a protective factor against atherosclerosis. However, the effects of CETP itself and its interaction with HDL-C have not been investigated in hemodialysis patients, who are at high risk for atherosclerosis and generally considered to have decreased reverse cholesterol transport. We investigated the independent or synergistic influence of postprandial serum CETP and HDL-C concentrations on apparent atherosclerotic complications in 202 hemodialysis patients aged 40 to 80 years. Patients with vascular disease (n = 39) had significantly lower concentrations of CETP than those without vascular disease (n = 163). When all study subjects were divided into four groups according to CETP and HDL-C concentrations based on median values, we found significant differences in the prevalence of vascular disease (test for trend, P < 0.005): 28.8% in group I (HDL-C < 48 mg/dL; CETP < 2.2 microgram/mL); 25.0% in group II (HDL-C < 48 mg/dL; CETP >/= 2.2 microgram/mL); 17.8% in group III (HDL-C >/= 48 mg/dL; CETP < 2.2 microgram/mL); and 6.9% in group IV (HDL-C >/= 48 mg/dL; CETP >/= 2.2 microgram/mL). Multiple logistic regression analysis retained the interaction term between HDL-C (in milligrams per deciliter) and CETP (in micrograms per milliliter), but not HDL-C or CETP itself, as inversely associated with vascular disease in the entire patient group. In patients with HDL-C levels at the median value or greater, CETP had an independent odds ratio of 0.31 (95% confidence interval, 0.1 to 0.97; P < 0.05) after adjusting for age. These results suggest that CETP may serve as a protective factor against vascular disease in hemodialysis patients, especially those with normal or elevated HDL-C concentrations.