OBJECTIVES: Randomized clinical trials, SALT-1 and SALT-2, showed that tolvaptan was an efficacious and safe therapy for the treatment of hyponatremic SIADH (Syndrome of Inappropriate Antidiuretic Hormone Secretion) and was associated with a reduction in the length of stay (LOS) in the hospital for SIADH patients.  This study evaluated the medical cost offsets associated with tolvaptan usage based on the SALT-1 and SALT-2 trials. METHODS: The Healthcare Cost and Utilization Project (HCUP) 2009 Nationwide Inpatient Sample (NIS) database was used to estimate LOS and hospital cost of SIADH patients (age ≥18 years) in the United States. A cost offset model was constructed and utilized to evaluate the impact of tolvaptan on hospital cost and LOS, with univariate and multivariate Monte Carlo sensitivity analyses. RESULTS: In the SALT-1 and SALT-2 trials, SIADH patients receiving tolvaptan had a shorter hospital LOS than placebo patients (4.98 vs. 6.19 days). From the HCUP NIS database, 21,718 SIADH hospitalizations were identified, with a mean LOS of 5.7 days and mean hospital costs of $8667. With an inpatient tolvaptan treatment duration of 4 days, the cost offset model estimated that tolvaptan usage was associated with a mean LOS reduction of 1.1 days and a hospital cost saving of $694 per admission. The cost reduction ranged from $355 to $1033 with variations of any single modeling parameter. 10,000 cycles of Monte Carlo simulation showed the 95% confidence interval for cost saving to be $73−$1,405, with 98.8% cycles having a positive net cost saving.  The total cost saving was estimated to be $15 million among the HCUP/SIADH population. CONCLUSIONS: Based on the SALT-1 and SALT-2 trials, tolvaptan usage versus placebo is associated with a shorter hospital LOS.  This study showed that tolvaptan usage versus placebo is additionally associated with lower hospital costs among hyponatremic SIADH patients in the United States.