Background: Chronic heart failure (CHF) impairs the heart’s pumping ability due to structural or functional abnormalities. It is a leading cause of death worldwide, with mortality rates of 10-50% based on severity. Risk stratification methods help predict CHF prognosis. ST2, an interleukin-1 receptor, is valuable for forecasting rehospitalization and cardiovascular events. In progressive heart failure, increased sST2 receptor expression inhibits the protective effects of IL-33, worsening the condition. Methods: Chronic heart failure patients with LVEF <40% were studied in a cohort design. After sST2 blood samples were taken, patients were followed for 1 year and 10 months to monitor Major Cardiovascular Events (MACEs) like rehospitalization and mortality. Baseline characteristics included demographic, clinical, comorbidity, laboratory, and echocardiographic data. The best sST2 cut-off was determined using ROC curves. Kaplan-Meier and Cox Regression analyses assessed outcomes using SPSS 26.0. Results: All 80 samples completed the study with no drop-outs. The optimal sST2 cut-off for predicting Major Cardiovascular Events (MACEs) was >19.38 ng/mL (AUC 0.668, CI 95% 0.542-0.794; p=0.023), with 66.7% sensitivity and 66.1% specificity. Survival analysis showed patients with sST2 ≥19.4 ng/mL had lower long-term survival (58.8% vs. 84.8%; p=0.007). Adjusted for age and comorbidities, high sST2 levels significantly predicted MACEs, with a 3.581 times higher risk (95% CI 1.343-9.551; p=0.011) of rehospitalization and mortality. Conclusion: High sST2 levels (≥19.4 ng/mL) were associated as a risk factor of rehospitalization and mortality in chronic heart failure patients with reduced ejection fraction.