Objective To investigate the effects of positive end-expiratory pressure (PEEP) setting of mechanical ventilation guided by esophageal pressure in the treatment of patients with traumatic craniocerebral injury combined with acute respiratory distress syndrome (ARDS). Methods The retrospective cohort study was conducted. From June 2016 to June 2018, 55 patients with traumatic craniocerebral injury combined with ARDS who met the inclusion criteria were admitted to Zhengzhou Central Hospital Affiliated to Zhengzhou University. According to PEEP setting method, 28 patients were allocated to esophageal pressure group (17 males and 11 females, aged (40±13) years) and 27 patients were allocated to PEEP-fractional concentration of inspired oxygen (FiO₂) table group (18 males and 9 females, aged (38±10) years). Patients in the 2 groups were treated with mechanical ventilation guided by lung protective ventilation strategy, and the optimal PEEP at 0 (immediately), 24, 48, and 72 h after treatment was determined according to esophageal pressure and PEEP-FiO₂ table, respectively. The mechanical ventilation parameters in the 2 groups were adjusted according to the optimal PEEP. The transpulmonary end-expiratory pressure, pulmonary compliance, oxygen index, central venous pressure, mean arterial pressure, and intracranial pressure at 24, 48, and 72 h after treatment were recorded. Data were statistically analyzed with analysis of variance for repeated measurement, chi-square test, independent sample

test, and Bonferroni correction. Results The optimal PEEP of patients in esophageal pressure group at 0, 24, 48, and 72 h after treatment was (12.4±3.9), (11.2±3.5), (13.4±2.6), and (13.2±3.6) cmH₂O (1 cmH₂O=0.098 kPa), respectively, which was significantly higher than (8.2±2.5), (7.4±2.2), (8.3±2.3), and (8.5±2.5) cmH₂O in PEEP-FiO₂ table group, respectively (

=4.702, 4.743, 7.849, 5.623

0.01). The transpulmonary end-expiratory pressure and pulmonary compliance at 24, 48, and 72 h after treatment and oxygen index at 48 and 72 h after treatment of patients in esophageal pressure group were significantly higher than those in PEEP-FiO₂ table group (

=17.852, 20.586, 19.532, 4.752, 5.256, 7.446, 2.342, 4.178,

<0.05 or

<0.01). The central venous pressure of patients in esophageal pressure group at 24, 48, and 72 h after treatment was significantly higher than that in PEEP-FiO₂ table group (

=12.632, 5.247, 8.994,

<0.01), and there was no statistically significant difference in mean arterial pressure of patients between the 2 groups at 24, 48, and 72 h after treatment (

>0.05). The intracranial pressure of patients in esophageal pressure group was higher than that in PEEP-FiO₂ table group at 24, 48, and 72 h after treatment, but there was no statistically significant difference between the 2 groups (

>0.05). Conclusions For patients with traumatic craniocerebral injury combined with ARDS, the optimal PEEP can be set under the guidance of esophageal pressure method, and the mechanical ventilation parameters adjusted according to the optimal PEEP can improve lung compliance and accelerate recovery of lung function more effectively, with no adverse effect in mean arterial pressure and intracranial pressure.