Background Monocyte differentiation antigen CD14 is considered an important cell-activating mediator of inflammatory responses that may result in atherosclerosis, coronary artery disease (CAD), thrombus formation, and myocardial infarction (MI). We assessed the possibility that a C → T nucleotide substitution polymorphism in the promoter (position −159) of the gene encoding CD14 constitutes a risk factor for CAD and MI. Methods Consecutive patients with significant, angiographically documented coronary stenoses but without symptoms or signs of old or acute MI constituted the group with CAD (n = 998). Consecutive patients with angiographic examination with old or acute MI constituted the group with MI (n = 793). Subjects matched with patients for age and gender but without angiographic evidence of CAD and without symptoms or signs of MI (n = 340) and a group of healthy blood donors (n = 104) served as controls. Results Genotype distributions of the −159C/T polymorphism were similar across the groups; CC:CT:TT was 26.9%:51.0%:22.1% in blood donors, 25.9%:52.0%:22.1% in matched control subjects, 27.4%:49.9%:22.7% in patients with CAD, and 29.2%:49.2%:21.6% in patients with MI. The lack of association persisted also after adjustment for the presence of conventional cardiovascular risk factors. In addition, no significant differences were found between genotype distributions of control subjects and selected subgroups of patients with CAD or MI. Conclusion These findings indicate that, in the sample of patients examined in this study, the −159C/T polymorphism of the CD14 gene is not related to CAD or MI. (Am Heart J 2002;143:971-6.)