Background: Alveoli tend to collapse in patients with acute respiratory distress syndrome (ARDS). Endotracheal aspiration may increase alveolar collapse due to the loss of end-expiratory lung volume (EELV). We aimed to compare the loss of EELV after open and closed suction in patients with ARDS. Methods: This randomized crossover study included 20 patients receiving invasive mechanical ventilation for ARDS. Open and closed suction were applied in a random order. Lung impedance was measured using electric impedance tomography. The change in end-expiratory lung impedance end of suction and at 1, 10, 20, and 30 min after suction, was used to represent the change in EELV. Arterial blood gas analyses and ventilatory parameters such as the plateau pressure (Pplat), driving pressure (Pdrive), and compliance of the respiratory system (CRS) were also recorded. Results: Less volume loss was noted after closed suction than after open suction (mean ΔEELI: −2661 ± 1937 vs. −4415 ± 2363; mean difference: −1753; 95% CI [−2662, −844]; P = 0.001). EELI returned to baseline 10 min after closed suction but did not return to baseline even 30 min after open suction. After closed suction, the Pplat and Pdrive decreased while the CRS increased. Conversely, the Pplat and Pdrive increased while the CRS decreased after open suction. Conclusions Endotracheal aspiration may result in alveolar collapse due to loss of EELV. Given that closed suction is associated with less volume loss at end-expiration without worsening ventilatory parameters, it should be chosen over open suction in patients with ARDS.