Hypertonic saline (HTS) may decrease intracranial pressure (ICP) in severe traumatic brain injury (STBI) and effectively resuscitates hypotensive patients. No data exist on institutional standardization of HTS for hypotensive patients with STBI. It remains unclear how HTS affects brain tissue oxygenation (PbtO2) in STBI. We hypothesized HTS could be safely standardized in patients with STBI and would lower ICP while improving cerebral perfusion pressure (CPP) and PbtO2. Under institutional guidelines in a Level I trauma center, 12 hypotensive STBI intensive care unit subjects received HTS. Inclusion criteria included mean arterial pressure (MAP) < or = 90 mmHg, Glasgow Coma Scale (GCS) < or = 8, ICP > or = 20 mmHg, and serum [Na+] <155 mEq/L. All patients underwent ICP monitoring. Hemodynamics, CPP, ICP, and PbtO2 data were collected before and hourly for 6 hours after HTS infusion. Guideline criteria compliance was greater than 95 per cent. No major complications occurred. Mean ICP levels dropped by 45 per cent (P < 0.01) and this drop persisted for 6 hours. CPP levels increased by 20 per cent (P < 0.05). PbtO2 remained persistently elevated for all time points after HTS infusion. Institutional use of HTS in STBI can be safely implemented in a center caring for neurotrauma patients. HTS infusion in hypotensive STBI reduces ICP and raises CPP. Brain tissue oxygenation tends to improve after HTS infusion.