Background: Bolus doses of 23.4% sodium chloride (NaCl) are commonly used for the treatment of intracranial hypertension; however, delays in administration may occur in patients without central intravenous access. At our institution, equiosmolar bolus doses of 5% NaCl have emerged as potential alternatives to 23.4% NaCl because they may be safely administered through peripheral lines. Objectives: We sought to assess the efficacy in reducing intracranial pressure (ICP), time to administration, and safety of 5% NaCl as compared with 23.4% NaCl for the treatment of intracranial hypertension. Methods: Patients admitted from July 2012 to June 2014 who received boluses of 5% NaCl or 23.4% NaCl for a sustained ICP >20 mm Hg were included. Data collected included measurements of ICP, time to administration, and adverse events. Results: A total of 44 patients were identified; 11 received 5% NaCl, and 33 received 23.4% NaCl. The median percentage reductions in ICP at 30, 60, and 120 minutes in patients who received 5% versus 23.4% NaCl were 34% versus 26% (P = 0.850), 48% versus 40% (P = 0.700), and 46% versus 30% (P = 0.064), respectively. The median time to administration was shorter in the 5% NaCl group (7 vs 11 minutes, P = 0.364). Both groups had a 27% rate of adverse events and no infusion site reactions. Conclusions: These data suggest that 5% NaCl may be as effective as 23.4% NaCl at lowering ICP if given at equiosmolar doses, has a shorter time to administration, and has no difference in the prevalence of adverse events.