The aim of the present study was to determine if prednisone, a glucocorticoid, added to conventional treatment for patients with decompensated congestive heart failure (DCHF) refractory to the conventional care, results in significant relief of congestive symptoms and improvement of clinical status. Diuretic-based strategies, as the mainstay in DCHF management, are not always effective in eliciting diuresis. However, the addition of prednisone to standard care may induce potent diuresis in this clinical setting. Thirty-five patients with DCHF were enrolled in the study, and prednisone (1 mg/kg/day with maximum dosage of 60 mg/day) was added to the standard treatment. Primary endpoints were the effects on daily urine volume, patient and physician assessed dyspnea and global clinical status, and changes in renal function. The addition of prednisone induced potent diuresis with time. As a result of the diuresis, congestive symptoms improved markedly in 80% and global clinical status improved markedly in 68.6% of the DCHF patients at the end of the study (P < 0.001). The change in serum creatinine from baseline was -12.21 micromol/L (P < 0.05). Adding prednisone to conventional care in the patients with refractory DCHF induced potent diuresis accompanied by a dramatic relief of congestive symptoms and improvements in clinical status and renal function.