Background: An endotracheal tube (ETT) which is required for any mechanical ventilation procedure, involves an inherent risk for facial skin, lip and mucosal pressure ulcers. The ETT is one of the most common devices associated with medical device-related pressure ulcers (MDRPUs) among surgical and intensive care unit patients. Methods: We investigated, for the first time in the literature, the biomechanical effects of the presence and positioning of an ETT in the mouth on lip, mucosal and surrounding facial skin loads. Using two anatomically-realistic finite element model variants, two ETT locations were simulated and compared, at the center versus the corner of the mouth. Results: A central location of the ETT inflicted greater lip and mucosal stress values, but a corner location caused a more widespread and diffused lip, mucosal and facial skin stress exposure. Accordingly, we cannot recommend a ‘safer’ location for ETTs in the mouth. Conclusion: Additional preventative measures such as dedicated dressing materials or special cushioning pads applied prophylactically, should be developed to protect from MDRPUs associated with ETT usage. The present modeling framework can be employed to study the biomechanical efficacy of such protective technologies, and can therefore aid in the prevention of ETT-caused MDRPUs.