To investigate the association between cyclin-dependent kinase inhibitor 2A (CDKN2A) gene, cyclin-dependent kinase inhibitor 2B (CDKN2B) gene, and methylthioadenosine phosphorylase (MTAP) gene and myocardial infarction (MI) in Chinese Hans.A total of 432 patients with MI and 430 controls were included in the study. Nine polymorphisms in the MTAP gene, two polymorphisms in the CDKN2A gene, and two polymorphisms in the CDKN2B gene were selected using a tagging single nucleotide polymorphism (tSNP) strategy.We observed that rs7027989 in the MTAP gene, and rs3217992 and rs1063192 in the CDKN2B gene were significantly associated with MI in male subjects. For rs7027989 and rs3217992, male subjects with the AA or AG genotypes had 1.26-fold and 1.24-fold increased risk of MI, respectively, compared with those with the GG genotype. For rs1063192, the G allele was associated with a reduced risk of MI with a per-allele OR of 0.71 in male subjects. The risk of rs7027989 and rs1063192 remained significant after adjusting for covariates.This study demonstrates for the first time that polymorphisms in CDKN2B and MTAP gene may influence the risk of MI in Chinese.