BackgroundAfter acute coronary syndrome (ACS), inflammation aids healing but may harm the heart. Interleukin (IL)‐18 and IL‐1β are pivotal proinflammatory cytokines released during pyroptosis, a process that initiates and sustains inflammation. This study aimed to evaluate the levels of circulating IL‐18 and IL‐1β during the progression of ACS and to determine their association with subsequent clinical events in ACS patients.HypothesisCirculating levels of IL‐18 and IL‐1β are associated with subsequent clinical events in ACS patients.MethodsEmploying immunoassays, we examined plasma levels of IL‐1β and IL‐18 in 159 ACS patients and matched them with 159 healthy controls. The primary composite endpoint included recurrent unstable angina, myocardial infarction, heart failure exacerbation, stroke, or cardiovascular death.ResultsACS patients exhibited a significant increase in plasma IL‐18 levels, measuring 6.36 [4.46−9.88] × 102 pg/mL, in contrast to the control group with levels at 4.04 [3.21−4.94] × 102 pg/mL (p < 0.001). Conversely, plasma levels of IL‐1β remained unchanged compared to the control group. Following a 25‐month follow‐up, IL‐18 levels exceeding the median remained an important prognostic factor for adverse clinical events in ACS patients (hazard ratio = 2.37, 95% confidence interval: 1.14−4.91, p = 0.021). Besides, IL‐18 displayed a nonlinear association with adverse clinical events (p nonlinear = 0.044). Subgroup analysis revealed that the correlation between IL‐18 and the risk of adverse clinical events was not significantly affected by factors such as age, sex, history of diabetes, smoking, Gensini score, or ACS type (all p interaction >0.05).ConclusionIL‐18 appears to hold potential as a predictive marker for anticipating clinical outcomes in patients with ACS.