Objective To investigate the risk factors of premature atherosclerotic three-vessel coronary artery dis?ease (CHD), and the association between single nucleotide polymorphism (SNP) of CD36 rs3211956, rs7755 and premature CHD. Methods Patient with premature three-vessel coronary artery disease (n=102) which were confirmed by consecutive coronary angiogram (lesion group) and patients (n=72) without CHD (control group) were enrolled in the study. Conventional CHD risk factors were compared between the two groups as well as SNPs of CD36 rs3211956 and rs7755 to disclose inde?pendent risk factor for CHD, which were measured by mass spectrometry. Results Among the conventional CHD risk fac?tors, male, HBP, high LDL-C, low HDL-C were independent risk factors of premature CHD. The GT genotype proportion of rs3211956 was significantly lower (χ2=8.042,P=0.005) in the lesion group than that in control group while the TT genotype proportion is significantly higher in lesion group compared with that in control group (χ2=6.191,P=0.014). Patients with the TT genotype have higher score of BMI than patients with GG or GT genotype (P=0.037). The G allele proportion of rs7755 in the lesion group was significantly higher than control group (χ2=3.636, P=0.047). Patients of the GG genotype have higher scores of BMI but lower level of HDL-C than those with AA or AG genotype (P<0.001). Logistic regression analysis re?vealed that after excluding a number of confounding factors, GG and TT genotype of rs3211956 and GG and GA genotype of rs7755 were respectively one of the independent risk factors for premature CHD. Conclusion The SNPs of CD36 rs7755 and rs3211956 may be the independent risk factors of premature coronary heart disease and might affect the the onset of CHD by affectting BMI and HDL-C.