A prospective observational study was conducted to evaluate the predictive value of interleukin-18 (IL-18) for major adverse cardiovascular events (MACEs) in hemodialysis patients. A total of 85 participants (45 hemodialysis patients and 40 healthy volunteers) with a mean age of 56.3 years were enrolled in this study. Demographic and clinical data were collected. MACE was used as the primary endpoint. Results showed that the hemodialysis patients had higher levels of IL-18 (701.6 ± 88.52 versus 152.0 ± 55.31 pg/mL, P < 0.01) and a high rate of MACE (15.6% versus 2.5%, P < 0.01) compared with healthy controls. Multiple linear regression analysis showed that the serum creatinine and left ventricular ejection fraction were significantly effective factors influencing IL-18 (P < 0.01). Receiver-operating characteristic curve analysis showed that IL-18 levels were better predictors for MACE. The area under the curve of IL-18 was 0.81 (0.70-0.92) (P = 0.004). IL-18 levels provided 87.5% sensitivity and 26% specificity with a threshold value of 534.5 pg/mL. Our findings indicated that hemodialysis patients with high levels of IL-18 had a high incidence rate of MACE. IL-18 is a good predictive marker of MACE in hemodialysis patients.