BACKGROUND: In traumatic brain injury (TBI) patients desmopressin administration may induce rapid decreases in serum sodium and increase intracranial pressure (ICP). AIM: In an international multi-centre study, we aimed to report changes in serum sodium and ICP after desmopressin administration in TBI patients. METHODS: We obtained data from 14 neurotrauma ICUs in Europe, Australia and UK for severe TBI patients (GCS ≤ 8) requiring ICP monitoring. We identified patients who received any desmopressin and recorded daily dose, 6-hourly serum sodium, and 6-hourly ICP. RESULTS: We studied 262 severe TBI patients. Of these, 39 patients (14.9%) received desmopressin. Median length of treatment with desmopressin was 1 [1-3] day and daily intravenous dose varied between centres from 0.125 to 10 mcg. The median hourly rate of decrease in serum sodium was low (- 0.1 [- 0.2 to 0.0] mmol/L/h) with a median period of decrease of 36 h. The proportion of 6-h periods in which the rate of natremia correction exceeded 0.5 mmol/L/h or 1 mmol/L/h was low, at 8% and 3%, respectively, and ICPs remained stable. After adjusting for IMPACT score and injury severity score, desmopressin administration was independently associated with increased 60-day mortality [HR of 1.83 (1.05-3.24) (p = 0.03)]. CONCLUSIONS: In severe TBI, desmopressin administration, potentially representing instances of diabetes insipidus is common and is independently associated with increased mortality. Desmopressin doses vary markedly among ICUs; however, the associated decrease in natremia rarely exceeds recommended rates and median ICP values remain unchanged. These findings support the notion that desmopressin therapy is safe.