Coronary heart disease (CHD) is a major health problem and a major cause of death in most countries. Evidence has been presented that gene polymorphisms (HindIII, PvuII and Ser447Ter) of lipoprotein lipase (LPL) are risk factors of coronary artery disease (CAD). Aim: Our objective of the present investigation was to determine whether 3 LPL polymorphisms (LPL-HindIII, LPL-PvuII and LPL-Ser447Ter) can be considered as independent risk factors for CAD in the Saudi population. Methods: We recruited 120 CAD subjects, confirmed angiographically with identical ethnic backgrounds and 65 control subjects. Polymerase chain reaction-restriction fragment length polymorphisms (RFLP) technique was used to detect the polymorphisms of the LPL gene. Results and conclusion: For the HindIII genotype, within the CAD group, the frequencies of the H+H+ were found in 50.8%, whereas 44.2% carried the H-H+ genotype, and 5% carried the H-H- genotype. Within the control group, the H+H+ genotype was found in 44.6%, whereas 35.4% carried the H-H+ genotype, 20% carried the H-H- genotype. The odds ratio (OR) of HindIII genotype H+H+ vs. H-H- genotype at 95% Confidence Interval (CI) were 4.6 (1.57-13.2) and p < 0.005, hence showing no significant association with CAD. For the P nu uII genotype, within the CAD group the frequencies of the P+P+ found in 41.7% whereas 43.3.2% carried the P-P+ genotype, and 15% carried the P-P- genotype. Within the control group the P+P+ was found in 38.5%, 43.0% carried the P-P+ genotype, and 18.5% carried the P-P- genotype. The OR of PvuII genotype P+P+ vs. P-P- genotypes (95% CI) is 1.33 and p = 0.52; hence, it was also insignificant to show association with the disease. For the Ser447Ter genotype, within the CAD group, the frequencies of the C/C found in 83.3%, whereas 16.7% carried the C/G genotype. Within the control group, the C/C was found in 87.7% and 12.3% carried the C/G genotype. We did not get any GG genotypes in control as well as patients for this gene. It can be concluded that C allele of gene masks the presence of G allele in the Saudi population. The OR of CG + GG vs. CC (95% CI) is 1.43 from 0.59 to 3.44 which is insignificant. Hence this gene also has no significant association with CAD in the Saudi population.