Aims: Currently, mannitol and hypertonic saline (HTS) are mostly used in treatment of adult with elevated intracranial pressure (ICP). However, there is no high-level evidence on the superiority of mannitol versus HTS. Therefore, a systematic review and meta-analysis was performed to compare effects of hypertonic saline and mannitol for treatment of adults with elevated ICP. Methods: We performed a search on lots of databases for eligible studies. Prospective randomized control trials comparing HTS and mannitol in adults with elevated ICP were included, and ICP monitoring should be applied. Primary outcome was change of ICP values, and secondary outcomes were changes of cerebral perfusion pressure (CPP), mean arterial pressure (MAP), heart rate, serum sodium, serum osmolarity and hematocrit (HCT). Results: A total of ten studies (384 patients, 1578 episodes) were included. A pooled result indicated HTS reduced ICP more effectively than mannitol. At 0.5 h, 1 h, and 2 h after intervention, results also showed a better efficiency of HTS than mannitol. In addition, results indicated elevation of CPP, serum sodium and serum osmolarity were all more in HTS group than in mannitol group. And there were no statistical significance in changes of MAP, HCT and HR between the two interventions. Conclusion: Our study indicated HTS had a better efficiency in reduction of elevated ICP than mannitol in earlier stage. Based on the current level of evidence of ICP control and effects in other physiological indicators, HTS could be recommended as a first-line agent for managing patients with elevated ICP.