MicroRNAs are associated with myocardial damage and heart failure (HF). The present study investigated whether the plasma levels of microRNA (miR)‑21, ‑126 and ‑423‑5p alter according to the (de)compensated state of patients with HF and are associated with all‑cause mortality. In 48 patients with HF admitted to the emergency room for an episode of acute decompensation, blood samples were collected to measure miR and B‑type natriuretic peptide levels within 24 h of hospital admission, at the time of hospital discharge, and a number of weeks post‑discharge (chronic stable compensated state). Levels of miR‑21, miR‑126 and miR‑423‑5p increased between admission and discharge, and decreased following clinical compensation. During follow‑up (up to 48 months), 38 patients (79%) were rehospitalized at least once and 21 patients (44%) succumbed. Patients who had increased levels of miR‑21 and miR‑126 at the time of clinical compensation exhibited better 24‑month survival and remained rehospitalization‑free for a longer period compared with those with low levels. Additionally, patients whose levels of miR‑423‑5p increased between admission and clinical compensation experienced fewer hospital readmissions in the 24 months following the time of clinical compensation compared with those who had decreased levels. It was concluded that the plasma levels of miR‑21, miR‑126 and miR‑423‑5p altered during clinical improvement and were associated with the prognosis of acute decompensated HF.