Heart failure is a leading cause of hospitalization, morbidity and mortality. Treatments are not up-titrated for all patients because of adverse effects. Strategies to better discriminate patients who may benefit most from titration are needed to improve the benefit-risk balance. Soluble suppression of tumorigenicity-2 (sST2) is a new prognostic biomarker of heart failure. Patients with a high baseline sST2 levels could benefit the most from cardioprotective treatments. The current study considered sST2 value as a guide for medical management in patients admitted for acute HF decompensation, in an attempt to minimize hospital readmission. STADE-HF (sST2 As a help for management of Diagnosis, Evaluation and management of HF) was a blinded prospective randomized controlled trial and included 123 patients admitted for heart failure between January 2017 and August 2018 for acute HF. There were randomized into 2 groups: Usual treatment group, in which patient's sST2 level was unknown, and interventional treatment group, for whom sST2 level was known and used on day 4 of hospitalization for guide the treatment. The main clinical endpoint was the readmission rate for any cause at 1 month. The primary endpoint of readmission during the first month follow-up was observed in 28 patients (25%); 10 patients (19%) in the usual group, and 18 (32%) in the sST2 group without statistical difference ( P = 0.11). The mean duration of hospitalization was lower in patients with low sST2 (< 37 ng/mL) at admission (8.5 ± 9.5 days vs. 14.8 ± 14.9 days when sST2 > 37 ng/mL, P = 0.003). The STADE-HF study failed to decrease readmissions for patients admitted for acute HF. A long-term follow-up is conducted to evaluate the effect on cardiovascular hospitalization and mortality at one year after index hospitalization.