Objective To investigate the titration of best positive end-expiratory pressure (Best PEEP) based on mechanical power (MP) and transpulmonary pressure monitoring during lung reexpansion in patients with acute respiratory distress syndrome (ARDS), and to analyze the value of both in evaluating the prognosis of ARDS patients.Methods ARDS patients treated in the intensive care Unit of the First Affiliated Hospital of Jinzhou Medical University from September 2021 to March 2023 were selected and divided into survival group and death group according to the 28-day mortality rate. After full sedation, esophageal pressure tube was inserted through the nasal passage, and lung recruitment maneuvers (RM) was performed by incremental PEEP method. The Best PEEP method was titrated based on MP and transpulmonary pressure. Pearson correlation analysis was used to analyze the correlation between MP at RM 30 min and 2 h and transpulmonary pressure. The changes of clinical indicators at 30 minutes and 2 hours after RM were compared between the two groups with different outcomes. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of 2 h MP and transpulmonary pressure for 28-day mortality in ARDS patients. Results MP and transpulmonary pressure in the survival group decreased significantly at 30 min and 2 h, while MP and transpulmonary pressure in the death group showed a significant upward trend (P < 0.05). The Best PEEP and RR at 30 min and 2 h of the RM in the survival group were lower than those in the death group (P < 0.05). Pearson correlation analysis showed that MP at RM 30 min and 2 h was significantly correlated with transpulmonary pressure (r = 0.710 and 0.804, P < 0.05). The area under the ROC curve of MP and transpulmonary pressure were 0.812 and 0.795, respectively. 95% confidencial interval: 0.704 - 0.920 and 0.687 - 0.903 (P < 0.05); The sensitivity was 86.95% and 82.50%, respectively. The specificity were 76.67% and 59.40%; The positive predictive values were 0.851 and 0.688; The negative predictive values were 0.793 and 0.759; The optimal cut-off values were 15.5 and 17.5, respectively. RM 2 h MP and transpulmonary pressure have good predictive value for 28-day mortality in ARDS patients. Conclusion Monitoring MP and transpulmonary pressure during lung recruitment maneuver can effectively guide the titration of Best PEEP in ARDS patients, and both have good evaluation value for the prognosis of ARDS patients.