Hyponatraemia (serum sodium concentration<135 mmol/L) is the most common electrolyte disorder in hospitalised patients. We analysed the safety and efficacy of tolvaptan in the treatment of hyponatraemia in hospitalised inpatients and report the first consecutive retrospective clinical case series report based on a single centre experience from the United Kingdom. We sought out the case records of all patients treated with tolvaptan for hyponatraemia over a period of 19 months; 15 episodes of treatment with tolvaptan in 14 patients were analysed. There were 8 women and 6 men (age 72 ± 16, (mean ± standard deviation), range 36 to 90 years, mean BMI 24.9 ± 8.67, 13.9 to 46.4 kg/m(2)). Thirteen patients were diagnosed with euvolaemic hyponatraemia. One patient had hypovolaemic hyponatraemia. The median duration of tolvaptan therapy was 3 days (1 to 21 days). A serum sodium level of 130 mmol/L was targeted during therapy and fluid restriction was discontinued. There was a significant change in sodium level from baseline (mean sodium 120.1 ± 4.6, 108-126 mmol/L) to cessation of tolvaptan therapy (mean sodium 131.9 ± 3.6, 125-139 mmol/L, P<0.0001). The maximum rate of change of sodium was observed in the first 24 hours of therapy (mean 6.7 ± 2.8, 1 to 11 mmol/L) with no patient exceeding 12 mmol/L in 24 hours and 18 mmol/L in 48 hours at any point whilst on tolvaptan. No patient developed the osmotic demyelination syndrome. Tolvaptan appears to be safe and effective in the management of hospitalised inpatients with definitive euvolaemic hyponatraemia when close monitoring is observed.