Hepatic lipase (LIPC) and cholesteryl ester transfer protein (CETP) are important components of high-density lipoprotein (HDL) metabolism and reverse cholesterol transport. Therefore, their genes are promising candidate genes for cardiovascular disease. The aim of the present study was to investigate whether combined LIPC -514C/T and CETP I405V polymorphisms correlate with angiographically documented coronary artery disease (CAD). Genotyping was performed in 317 patients who underwent clinically indicated coronary angiography. The patients were classified with significantly diseased arteries if one or more coronary arteries had a stenosis >50% and with minimally diseased arteries if there was no significant stenosis (<40%) in any artery. There were no significant associations of individual polymorphisms with the risk of significant CAD. In a multivariate logistic regression analysis including cardiovascular risk factors, simultaneous presence of both LIPC -514T and CETP 405V alleles was an independent predictor of significantly diseased arteries (odds ratio = 2.04; p = 0.022). This association was not significant in women with combined genotype who had the highest HDL-cholesterol. In conclusion, the combined T allele of LIPC -514C/T and V allele of CETP I405V are associated with the risk of CAD. Further, the higher HDL-cholesterol and female gender may reduce the effect of combined genotype on CAD risk.