Effective fixation of endotracheal tube is essential to prevent displacement, unplanned extubation, and pressure injuries (PIs), which remain common complications with traditional fixation methods. Advances in 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 aimed to design and evaluate the effectiveness of an endotracheal tube fixation device using 3D printing technology in patients receiving mechanical ventilation. We designed and manufactured the device and conducted a finite element mechanical analysis. In a single-center prospective non-concurrent controlled cohort trial, patients with an expected duration of mechanical ventilation exceeding 24 hours were stratified into the observation group (3D-printing device) and control group (traditional device) based on the order of hospital admission. The primary endpoints were tracheal tube displacement and unplanned endotracheal extubation (UEE). Ultimately, 51 patients from the observation group and 97 from the control group were subjected to statistical analysis. The incidence of endotracheal tube displacement was 1/51(1.9%) in observation group versus 12/97(12.4%) in control group (OR 6.28, 95%CI (1.91-21.05)), yielding a 99% probability of benefit. 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% probability of benefit. 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% probability of benefit. The observation group exhibited significantly higher nurse satisfaction scores compared with the control group (P=0.015). There were no significant differences in facial PI between the two groups. These findings suggest that the 3D-printing device reduced the incidence of tracheal tube displacement, UEE and lip PI, while improving nurse satisfaction.