Background: Endotracheal suctioning is associated with complications that include bleeding, infection, hypoxemia, cardiovascular instability, and tracheal mucosal injury. Recently, a closed-suction catheter with a pressure valve (Acetrachcare, AceMedical Co., Republic of Korea) was developed. We hypothesized that this new catheter might reduce tracheal mucosal injury compared to a conventional closed-suction catheter (Trachcare, Kimberly-balla RD, USA). Methods: This prospective, randomized study enrolled medical and surgical patients who required mechanical ventilation for more than 48 hours. Patients were randomized into two groups: one group was suctioned with the conventional closed-suction catheter (CCC) and the other group was suctioned with the closed-suction catheter with pressure valve (CCPV). Bronchoscopy was performed 48 hours later, and the severity of tracheal mucosal injury was graded on a 5-point scale, as follows: 0 = normal; 1 = erythema or edema; 2 = erosion; 3 = hemorrhage; and 4 = ulceration or necrosis. Results: A total of 76 patients (37 with CCPV and 39 with CCC) were included. There were no significant differences between the groups regarding demographic characteristics, changes in hemodynamic parameters during suction, incidence of pneumonia, length of intensive care unit (ICU) stay, or ICU mortality. On bronchoscopic evaluation, the use of the CCPV led to a significant decrease in tracheal mucosal injury (median tracheal mucosal injury grade 1 [IQR 0-1] vs. 2 [IQR 1-3], p = 0.001). Conclusions: We conclude that the novel closed-suction catheter with pressure valve may reduce tracheal mucosal injury compared to conventional catheters.