The roles of endothelial nitric oxide synthase gene polymorphisms in coronary artery disease have been intensively analyzed, with inconsistent results. Therefore, we performed this study to better assess the relationship between endothelial nitric oxide synthase genetic variations and the risk of coronary artery disease. Eligible studies were searched in PubMed, Medline, Embase, and Web of Science. Odds ratios with 95% confidence intervals were used to evaluate associations between endothelial nitric oxide synthase polymorphisms and coronary artery disease. A total of 132 genetic association studies were finally included. Significant associations with the risk of coronary artery disease were detected for the rs891512, rs1799983, rs2070744, rs11771443 and rs869109213 polymorphisms. Further subgroup analyses according to ethnicity of participants revealed that the rs1799983 and rs2070744 polymorphisms were significantly associated with the risk of coronary artery disease in both Caucasians and Asians, whereas the rs869109213 polymorphism was only associated with the risk of coronary artery disease in Caucasians. When we stratified data based on type of disease, we found that the rs1799983, rs2070744 and rs869109213 polymorphisms were all significantly correlated with the risk of myocardial infarction or acute coronary syndrome in certain genetic models. In conclusion, our findings indicate that the rs891512, rs1799983, rs2070744, rs11771443 and rs869109213 polymorphisms may serve as genetic biomarkers of coronary artery disease.