Background: This study aimed to compare pressure regulated volume control (PRVC) and synchronized intermittent mechanical ventilation (SIMV) modes of ventilation according to respiratory and hemodynamic stability in patients with traumatic brain injury (TBI) admitted to Intensive Care Unit (ICU). Materials and Methods: In a randomized, single-blinded, clinical trial study, 100 patients who hospitalized in ICU due to TBI were selected and randomly divided into two groups. The first and second groups were ventilated by PRVC and SIMV modes, respectively. During mechanical ventilation, arterial blood gas and respiratory and hemodynamic parameters were also recorded and compared between the two groups. Results: According to the t-test, the mean rapid shallow breathing index (RSBI) after the first 8 h of mechanical ventilation was significantly higher in SIMV group compared with PRVC group (107.6 ± 2.75 vs. 102.2 ± 5.2, respectively, P< 0.0001). Further, according to ANOVA with repeated measures, the trend of RSBI changes had a significant difference between the two groups (P < 0.001). The trend of ratio of partial pressure arterial oxygen and fraction of inspired oxygen was different between the two groups according to Mann–Whitney–Wilcoxon test (P < 0.001). Conclusions: Using PRVC mode might be more desirable than using SIMV mode in patients with TBI due to better stability of ventilation and oxygenating. To ensure for more advantages of PRVC mode, further studies with longer follow-up and more detailed measurements are recommended.