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Background We aimed to systematically review the efficacy of mannitol (MTL) on patients with acute severe traumatic brain injury (TBI).Methods Databases such as PubMed (US National Library of Medicine), CENTRAL (The Cochrane Library 2014, Issue 3), ISI (Web of Science: Science Citation Index Expanded), Chinese Biomedicine Database (CBM), and China Knowledge Resource Integrated Database (CNKI) have been searched for relevant studies published between 1 January 2003 and 1 October 2014.We have established inclusion and exclusion criteria to identify RCTs, which were suitable to be enrolled in the systematic review.The comparison group could be hypertonic saline (HS), hydroxyethyl starch, or others.The quality assessment was based on the Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.1 and modified Jadad score scale.The major outcome was mortality, followed by the secondary outcomes such as neurological outcome, days on intensive care unit (ICU), and ventilator day.In addition, intracranial pressure (ICP), cerebral perfusion pressure (CPP), and mean arterial pressure (MAP) were used as the surrogate endpoints.Data synthesis and meta-analysis was conducted by using R (version 3.7-0.).