Plasma lactoferrin concentrations are increased in patients with coronary artery stenosis. We investigated the effects of LTF gene polymorphisms in 305 healthy blood donors and their associations with coronary artery stenosis in 236 patients admitted for coronary angiography. Lactoferrin concentrations were determined by enzyme immunoassay. Genotyping was performed by polymerase chain reaction and DNA sequencing of LTF exons 2 and 4. In the blood donors, the deletion variant of rs10662431 and the G allele of rs1126478 were associated with higher plasma lactoferrin concentrations. The G allele of rs1126478 was more frequent in patients with significant coronary artery stenosis (p = 0.018, p value limit for significance by permutation = 0.030). The association remained significant in logistic regression with adjustment for clinical risk factors (odds ratio 2.485 [95% confidence interval 1.116-5.536], p = 0.026), but was weakened upon the inclusion of plasma lactoferrin (odds ratio 2.295 [0.949-5.550], p = 0.064). Current evidence indicates that rs1126478 affects the antibacterial effect of lactoferrin and that lactoferrin is involved in lipid metabolism. The relationships among lactoferrin genotypes, lactoferrin concentrations, and clinical factors on the risk for atherosclerosis are not fully understood, but the G allele of rs1126478 seems to have a detrimental effect in a European population.