Serum total sialic acid has recently been shown to be a cardiovascular risk factor. Increased levels of this substance are associated with higher cardiovascular mortality and with cerebrovascular disease. It has also been shown that serum concentrations of total and lipid-associated sialic acid are significantly increased in hypertriglyceridemia. On the other hand, several circulating lipoproteins have been suggested to be related to the severity of coronary atherosclerosis, but contradictory results have been reported in the possible relationship between the concentrations of sialic acid and the severity of coronary lesions in patients with coronary heart disease. The purpose of this study was to investigate the possible relationship between serum total sialic acid concentration, recently shown to be a cardiovascular risk factor, and serum lipid-bound sialic acid concentration and the severity of coronary lesions. The study comprised 90 subjects, divided into three subgroups according to angiography results: 30 patients with no vessel disease, 30 patients with single-vessel disease, and 30 patients with double/triple-vessel disease. Serum total sialic acid determination was carried out with the thiobarbituric acid method of Warren; lipid-associated sialic acid was assayed with the method of Katopodis. Mean serum total sialic acid levels in patients with single-vessel disease (P <.05) and patients with double/triple-vessel disease (P <.001) were found to be significantly increased compared with that in patients with no vessel disease, whereas mean serum lipid-bound sialic acid levels were found to be significantly different between patients with double- or triple-vessel disease and patients with no vessel disease (P <.001). We also noted a significant difference between the levels of serum total sialic acid (P <.001) and lipid-bound sialic acid (P <.001) in patients with single-vessel disease and patients with double/triple-vessel disease. We found a significant correlation only between serum lipid-bound sialic acid and coronary angiographic score in patients with double/triple-vessel disease (r = 0.425, P <.05). Although the concentration of serum total sialic acid is increased proportionally with the number of diseased coronary arteries, only the concentration of serum lipid-bound sialic acid is related to the severity of coronary atherosclerosis, especially in patients with double/triple-vessel disease. (J Lab Clin Med 2002;140:110-8)