Thirty-three subjects requiring hospitalization for acute congestive heart failure, and a serum sodium < 135 mmol/L, were randomized to tolvaptan 30 mg orally daily or furosemide 5 mg/h intravenously for initial 24 h, after which treatments could be escalated. Median daily dose throughout was tolvaptan 30 mg and furosemide 120 mg, with four subjects in each group requiring dose escalation. Urine output and net fluid balance were not different between groups at 24 h or subsequent time points up to 96 h. Changes in estimated glomerular filtration rate were comparable. Cystatin C im- proved at 24 h with tolvaptan compared with furosemide (6.4 ± 11.8 vs. 4.1 ± 17.2% change, P = 0.036), but the effect was transient. No significant between group differences were seen for NT-proBNP, plasma renin activity, or urinary neutrophil gelatinase-associated lipocalin:Cr. Serum sodium, as well as copeptin levels, increased with tolvaptan compared with furosemide.