The purpose of this study was to investigate the association of long non-coding RNA (lncRNA) ANRIL expression with disease risk, severity, inflammation level and prognosis of coronary artery disease (CAD). A total of 169 patients with unexplained chest pain or CAD-like symptoms underwent coronary angiography and were consecutively recruited, among whom 92 patients were diagnosed with CAD and were included in the CAD group while the other 77 patients were included in the control group. Plasma lncRNA ANRIL level of all patients was detected by quantitative polymerase chain reaction, Gensini score was evaluated via Gensini criterion. In CAD patients, plasma level of inflammatory factors was evaluated by enzyme linked immunosorbent assay, and overall survival (OS) was calculated. Plasma level of lncRNA ANRIL was increased in the CAD group compared to control group (P < 0.001) and disclosed a good predictive value for CAD risk (AUC=0.806, 95% CI: 0.741-0.871). In CAD patients, lncRNA ANRIL was positively correlated with Gensini score (r=0.270, P=0.009), high-sensitivity C-reactive protein level (r=0.293, P=0.005), tumor necrosis factor-alpha level (r=0.271, P=0.009) and interleukin (IL)-6 level (r=0.464, P < 0.001) while negatively associated with IL-10 (r=-0.274, P=0.008) level. Additionally, the OS was poorer in CAD patients with high lncRNA ANRIL expression compared to patients with low lncRNA ANRIL expression (P=0.025). In conclusion, Circulating lncRNA ANRIL expression associates with increased disease risk, severity, inflammation level and poor prognosis of CAD.