Airway management of adult patients with recessive dystrophic epidermolysis bullosa presents significant challenges associated with tissue fragility and distortion of airway anatomy. This retrospective case series describes 11 adult patients with recessive dystrophic epidermolysis bullosa and difficult airways undergoing 24 general anesthetics in which transnasal humidified rapid-insufflation ventilatory exchange was used for preoxygenation and apneic oxygenation. Despite an average time to intubation of over 6 minutes, transnasal humidified rapid-insufflation ventilatory exchange provided oxygenation before endotracheal intubation without the need for bag-mask ventilation or supraglottic airway ventilation, facilitating smooth and atraumatic flexible scope intubation. There were no major adverse events.