BACKGROUND Interleukin-18 (IL-18) is an inflammatory marker with challenging role in atherosclerosis. The present study was carried out aiming to evaluate the association between IL-18 serum level and extent and severity of atherosclerosis among young patients with unstable angina (UA) who underwent coronary angiography. METHODS This cross sectional study was performed from July to October 2015 in Chamran heart center, Isfahan, Iran. 180 patients with UA in the age range of below 50 years entered the study. All demographic, past history, physical examination, electrocardiogram (EKG or ECG), and transthoracic echocardiogram (TTE) data were collected. Serum level of IL-18 was measured using enzyme-linked immunosorbent assay (ELISA) method. A coronary angiography was performed on all patients to evaluate the presence and the incidence rate of coronary artery disease (CAD). RESULTS Mean age of the patients was 46.0 ± 4.6 years [47.4 ± 4.3 and 45.9 ± 4.9 among patients with CAD and normal coronary, respectively (P = 0.040)]. Rate of severe CAD was greater among men compared to women with values 67.8% and 51.8%, respectively (P = 0.032). The median [interquartile range (IQR)] value of serum IL-18 among patients with CAD [192.86 (128.03,325.75)] was higher than normal coronary subjects [172.81 (139.77,243.21)], however it was not significant (198.4 ± 93.5, P = 0.287). A significant difference between serum IL-18 level and number of stenosis vessels was detected only among women (P = 0.032). CONCLUSIONS Serum IL-18 level can predict the number of coronary arteries with significant stenosis among women with unstable angina.