Abstract Every year in the United States, nearly 500,000 patients develop an infection on a ventilator, of which an estimated 1 in 3 die. Ventilator-associated infections are the leading cause of mortality in the ICU and add $8B to US healthcare spending annually. Caring for patients on ventilators is multifactorial, but the driver of infection is silent aspiration (harmful fluid entering the airway without a patient response like coughing). Endotracheal tubes (ETTs) facilitate mechanical ventilation, and patients must rely on ETTs to prevent aspiration. For the last 50 years, ETTs have used an inflatable balloon to create a seal in the airway to prevent silent aspiration. The problem is that these balloons often fail by creasing, deflating, or migrating, which allows harmful fluid to enter the lungs, increasing the risk of infection for ventilated patients. To solve this problem, Respair developed RelianceET, an ETT that replaces the error- prone balloon with ultra-soft baffles (thin, flexible discs). The baffles gently fold along the trachea wall to comprehensively seal the airway while exerting less force than a balloon. In preliminary testing, RelianceET was 98% more effective than current ETTs in preventing leaks. Respair conducted over 100 interviews with clinicians and purchasers to map the needs of key stakeholders. Respair also met with FDA to validate novel safety test protocols for this SBIR. What remains unknown is if the baffle sealing mechanism is safe and effective across adult airway sizes. This SBIR has two specific aims to achieve critical milestones that assess the feasibility of RelianceET in adult airways. Aim 1: Complete comprehensive leak, tracheal force, and ventilatory pressure tests on prototypes in preparation for FDA submission. Respair will test RelianceET prototypes using novel protocols to quantify critical safety metrics that validate the baffle sealing mechanism across adult airway sizes. Aim 2: Evaluate the insertion and removal forces of ETTs on a novel benchtop model that includes the larynx (vocal folds) and trachea. Respair will develop and use 3D-printed airway models to compare the insertion and removal forces of RelianceET versus current ETTs. The models also quantify forces exerted on the vocal folds. During interviews, Respair found that comparative force data is required to convince stakeholders. Completing these objectives will validate RelianceET’s technical feasibility and safety, enabling Respair to reach a final design freeze. Respair aims to create a new standard for critical care by commercializing a safer and more effective endotracheal tube to improve outcomes for vulnerable patients on ventilators.