This study aimed at compare influences of airway pressure release ventilation (APRV) and Synchronized Intermittent Mechanical Ventilation (SIMV) on intracranial pressure and oxygenation status in patients with traumatic brain injuries. A clinical trial was carried out in 40 patients with traumatic brain injuries in the intensive care unit in Kamyab neurosurgery Hospital, Mashhad, Iran. The patients meeting the study inclusion criteria were randomly assigned into two groups; intervention (APRV, n= 20) and control (SIMV, n= 20). The ICP, CPP, MAP, PaO2, SPO2, PaO2/FIO2 in both groups were measured before and after conditioning. Analysis of data was done using independent t-test in SPSS V.22. The mean ICP remained unchanged in both groups (P= 0.421). After the intervention, the CPP, MAP, heart rate, and pulse pressure in APRV group were not significantly different compared with those in the two groups before the intervention (P> 0.05), PaO2, SPO2, PaO2/FIO2 in APRV group were significantly improved. The results showed APRV as a safe mode that can be beneficial in patients with traumatic brain injury without concerns for increased intracranial pressure.