Studies investigating the effect of trunk inclination on respiratory mechanics in mechanically ventilated patients with ARDS have reported postural differences in partition respiratory mechanics. Compared with more upright positions, the supine-flat position provided lower lung and chest wall elastance, allowing reduced driving pressures and end-inspiratory transpulmonary pressure. However, the effect of trunk inclination on respiratory mechanics in patients with obesity and ARDS is uncertain. Does the effect of change in posture on partition respiratory mechanics differ between patients with ARDS with and without obesity? In this single-center study, patients with ARDS with and without obesity were randomized into two 15-minute steps in which trunk inclination was changed from semi-recumbent (40° head up) to supine-flat (0°), or vice versa. At the end of each step partition respiratory mechanics, airway opening pressure and arterial blood gases were measured. Paired t test was used to examine respiratory mechanics and blood gas variables in each group. Forty consecutive patients were enrolled. Twenty were obese (BMI, 38.4 [34.5-42.3]), and 20 were non-obese (BMI, 26.6 [25.2-28.5]). In the patients with obesity, lung and chest wall elastance, driving pressure, inspiratory transpulmonary pressure, Paco2, and ventilatory ratio were lower supine than semi-recumbent (P< .001). Airways resistance was greater supine (P= .006). In the patients without obesity, only chest wall elastance was lower in supine vssemi-recumbent (P< .001). In mechanically ventilated patients with ARDS and obesity, supine posture provided lower lung and chest wall elastance, and better CO2 clearance, than the semi-recumbent posture. This study was registered with Australian New Zealand Clinical Trials Registry (ACTRN12623000794606).