Beitler JR, et al. - In this randomized clinical trial, researchers assessed the efficacy of positive end-expiratory pressure (PEEP) titration guided by esophageal pressure (P_ES), an estimate of pleural pressure, vs empirical high PEEP–fraction of inspired oxygen (F_io2) in moderate to severe acute respiratory distress syndrome (ARDS). Among 200 included patients, PEEP titration guided by P_ES measurement, compared with empirical high PEEP-F_io2 titration, led to no marked difference in a composite outcome that incorporated death and days free from mechanical ventilation through day 28. To guide PEEP titration in patients with moderate to severe ARDS, use of P_ES measurements, instead of an empirical high PEEP-F_io2strategy was not supported.