Small non‑coding microRNAs (miRNAs) are not only important for heart and vascular development but are also important in cardiovascular pathophysiology and diseases, such as ischemia and atherosclerosis‑related diseases. However, the effect of miR‑146a, miR‑149, miR‑196a2 and miR‑499 polymorphisms on coronary artery disease (CAD) susceptibility remain unknown. The aim of the present study was to examine the genotype frequencies of miR‑146a, miR‑149, miR‑196a2 and miR‑499 polymorphisms in patients with CAD, and assess their clinical applications for diagnosing and monitoring CAD. Using polymerase chain reaction‑amplified DNA, microRNA polymorphisms were analyzed in 522 patients with CAD and 535 control subjects. The miR‑149 rs2292832 C>T and miR‑196a2 rs11614913 T>C polymorphisms were shown to be significantly associated with CAD prevalence. In subgroup analyses according to disease severity, the miR‑146a rs2910164GG genotype was significantly associated with CAD risk in the stent ≥2 group. In addition, miR‑146aG/‑149T/‑196a2C/‑499 G allele combination was significantly associated with CAD prevalence (G‑T‑C‑G and G‑C‑C‑G of miR‑146a/‑149/‑196a2/‑499). The combination genotypes of miR‑146aGG/149TC+CC and miR‑149CC/196a2TC were significantly associated with CAD incidence. In subgroup analyses, miR‑146a rs2910164 C>G increased the risk of developing CAD in non‑smoking, hypertensive and nondiabetic subgroups. Furthermore, miR‑149 rs2292832 C>T and miR‑196a2 rs11614913 T>C was shown to increase CAD risk in females and patients aged >63 years old. The miR‑149T allele, miR‑196a2C allele and miR‑146aG/‑149T/‑196a2C/‑499 G allele combination were associated with CAD pathogenesis. The combined effects of environmental factor and genotype combination of miRNA polymorphisms may contribute to CAD prevalence.