Effective fixation of the endotracheal tube is essential to prevent displacement, unplanned extubation, and pressure injuries (PIs), which remain common complications with traditional fixation methods. Advances in three-dimensional (3D) printing technology offer opportunities to design personalized devices that may improve airway security and patient outcomes. However, no prior study has evaluated the use of 3D-printed fixation devices as an alternative to traditional methods. We aim to design and evaluate the effectiveness of an endotracheal tube fixation device produced using 3D printing technology in patients receiving mechanical ventilation. In a single-center, prospective, non-concurrent, controlled cohort trial, patients with an expected duration of mechanical ventilation exceeding 24 hours were stratified into an observation group (using a 3D-printed device; n = 51) and a control group (using a traditional device; n = 97). The primary endpoints were tracheal tube displacement and unplanned endotracheal extubation (UEE). The incidence of endotracheal tube displacement was 1/51 (1.9%) in the observation group vs. 12/97 (12.4%) in the control group (odds ratio [OR]: 6.28, 95% confidence interval [CI]: 1.91–21.05), yielding a 99% probability of benefit (POB). UEE incidence was 0/51 in the observation group, whereas it was 4/97 (4.1%) in the control group (OR: 5.26, 95% CI: 1.08–26.31), yielding a 98% POB. Lip PI occurred in 0/51 patients in the observation group vs. 10/97 (10.3%) patients in the control group (OR: 8.72, 95% CI: 2.11–35.98), yielding a 99% POB. The observation group exhibited significantly higher nurse satisfaction scores compared to the control group (p = 0.015). There were no significant differences in facial PI between the two groups. These findings suggest that the 3D-printed device reduced the incidence of tracheal tube displacement, UEE, and lip PI, while improving nurse satisfaction.