Background: Heart failure (HF) is a serious consequence that can have varying effects on newborns and children with congenital heart disease (CHD). The soluble isoform of tumor suppression-2 (sST2) has become an interesting promising biomarker of heart failure. The aim of this study was to prove the prognostic role of the soluble suppression of tumorigenicity-2 marker in the early prediction of heart failure in children with congenital heart disease and to correlate its levels with many clinical and echocardiographic issues. Subjects and methods: This case-control study was conducted at the Pediatrics Department, Faculty of Medicine, Zagazig University, on 36 pediatric patients; Patients were allocated into two equal groups; Cases group include 18 patients presented with manifestations of HF complicating CHD and the control group include 18 healthy individuals age & sex matched. Results: The levels of sST were significantly higher in the cases group than in the controls (p<0.001). ROC curve analysis revealed that sST2 cutoff point 30.55 ng/ml; with sensitivity to predict HF in children was 94.4% and with a specificity of 100%. There was a statistically significant positive correlation between sST2 levels and Mitral and Tricuspid E/é, TR, and PASP among the diseased group. In addition, there was a statistically significant negative correlation between the level of sST2 and FS, EF, and Mitral s among the diseased group. Conclusion; Soluble suppression of tumorigenicity-2 could be promising as early predictive and diagnostic biomarker of heart failure in congenital heart disease children.