Severe traumatic Brain Injury (STBI) is defined as a brain injury resulting in a loss of consciousness of greater than 6 hours and a Glasgow Coma Scale of 3 to 8. 1 STBI represents a significant medical problem, affecting over 10 million people in the global population annually.2 Cardinal manifestations of STBI are cerebral oedema and elevated intracranial pressure(ICP). Unless resolved, these symptoms may adversely affect outcome leading to morbidity and mortality. 3-8 Hence, control of sustained elevated ICP (defined as ICP>20mmHg for longer than 5 minutes) is the backbone of treatment. 9 Hyperosmolar therapy is used to treat cerebral oedema and elevated ICP. This therapy increases the osmolality of blood and causes the movement of fluid from cerebral tissue into the vessels across the intact blood brain barrier. Most commonly, Mannitol and Hyptertonic Saline(HTS) are used as the hyperosmolar agents. 10-12 Mannitol is used as de facto gold standard since years while Hypertonic Saline (HTS) is given as a second line therapy to patient unresponsive to Mannitol therapy 13,14 Mannitol therapy shows risks of rebound rise in ICP, renal failure and hypovolemia 15-17 and has thus led to interest in other agents like HTS, whose use has not been associated with significant neurologic, cardiac or renal side effects. 18-21 And while prior RCTs have suggested HTS to be more superior, the impact of these studies have been limited due to small number and size of the trials included. 22-26 Hence, this calls for a network meta-analysis where direct comparison of interventions within RCTs as well as indirect comparison using common comparators for HTS and Mannitol drug therapy is carried out on a larger scale to generate highest level of scientific evidence.