Laryngeal and tracheal morbidity is a common complication of endotracheal tube (ETT)-based airway management, and manifests as local irritation, inflammation, and edema. Systemic corticosteroids are commonly administered to manage these conditions; however, their efficacy is inadequate and limited by potential severe side effects. In the present study, a steroid delivery system for local therapy was developed to generate relatively high local drug concentrations and to improve drug efficacy. ETTs were coated with electrospun poly (lactic-co-glycolic acid) (PLGA) nanofibers loaded with mometasone furoate (MF), creating a microscale thick layer. MF exhibited sustained release from coated ETTs over 14 days in vitro. An in vivo efficacy study in rats demonstrated the therapeutic benefit of MF-coated ETTs over bare ETTs, as measured by reduced laryngeal mucosal thickness and submucosal laryngeal edema. The fiber coating remained intact during tube intubation and extubation, demonstrating good adhesion to the tubes even after 24 h in aqueous solution at 37 °C. These findings demonstrate the potential of drug-loaded ETTs to revolutionize the standard of care for endotracheal intubation.