Objective:To evaluate the effect of airway driving pressure (ΔP) guided sedation strategy on the prognosis of patients with mechanical ventilation.Methods:Patients who needed invasive mechanical ventilation and admitted to the department of intensive care unit (ICU) of Jiangxi Provincial People's Hospital from January 2017 to December 2018 were enrolled. The patients were divided into study group and control group according to the random number table. After informed consent of patients or their families, both groups received routine treatment in ICU. The control group was treated with light sedation strategy, the Richmond agitation sedation score (RASS) was performed every 4 hours, and the target was RASS > -3. ΔP in the study group was measured once a day, and the sedative target of patients with low driving pressure (ΔP ≤ 14 cmH 2O, 1 cmH 2O = 0.098 kPa) was RASS > -3, while the patients with high driving pressure (ΔP > 14 cmH 2O) was RASS ≤ -3. The evaluation was conducted at 28 days after admission to ICU, and the patients were followed up to 60 days. The main outcome was days without mechanical ventilation in 28 days. The secondary outcomes were the rate of extubation, discharge outcome, incidence of ventilator associated pneumonia (VAP) and delirium, and 60-day survival rate. Results:A total of 60 patients with respiratory failure due to various reasons were recruited, 30 in each group. There was no significant difference in gender, age, primary disease, severity of disease or ΔP between the two groups. The days without mechanical ventilation within 28 days in the study group were significantly more than that in the control group [days: 20 (0, 23) vs. 12 (0, 16), P = 0.018], and the incidences of VAP (3.3% vs. 16.7%, P = 0.045) and delirium (0% vs. 10.0%, P = 0.038) were significantly lower than that in the control group. There were no significant differences in the rate of extubation (73.3% vs. 66.7%, P = 0.273), discharge outcome [improvement (cases): 24 vs. 21, unhealed (cases): 2 vs. 5, deaths (cases): 4 vs. 4, P = 0.506] and 60-day survival rate (83.3% vs. 76.7%, P = 0.519) between the study group and control group. Conclusion:Compared with light sedation strategy, ΔP directed sedation strategy can effectively shorten the duration of mechanical ventilation and reduce the incidence of VAP and delirium in the ICU patients.