Objective: The aim of this study was to explore the effects of NINJ2 polymorphisms on susceptibility of coronary heart disease (CHD).Methods: We conducted a case-control study with 499 CHD cases and 505 age- and sex- matched controls. Five single nucleotide polymorphisms (SNP) in NINJ2 (rs118050317, rs75750647, rs7307242, rs10849390 and rs11610368) were genotyped by Agena MassARRAY platform. Odd ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression to assess the association of NINJ2 polymorphism and CHD risk adjusting for age and gender..Results: NINJ2 rs118050317 significantly increased the risk of CHD in people over 60 years old (allele: P = 0.010; heterozygote: P = 0.016; dominant: P = 0.015; additive: P = 0.021) and women (allele: P = 0.026; heterozygote: P = 0.015; dominant: P = 0.018; additive: P = 0.030). Rs118050317 and rs7307242 were closely related to the risk of hypertension in CHD patients. Additionally, rs75750647 significantly increased diabetes risk in multiple models among CHD cases (allele: P = 0.014; homozygote: P = 0.037; heterozygote: P = 0.044; dominant: P = 0.019; additive: P = 0.013), whereas rs10849390 could protect CHD patients from diabetes in allele (P = 0.035), homozygote (P = 0.047) and additive (P = 0.037) models. We also observed two block (block 1: rs118050317 and rs75750647; block 2: rs7307242, rs10849390 and rs11610368) in NINJ2.Conclusion: Our results suggested that the relationships of NINJ2 polymorphisms and CHD risk were dependent on age, sex or complications.