BACKGROUND: Negative-pressure pulmonary edema (NPPE) often develops with upper airway obstruction, and is uncommon in secured airways, for example, after tracheostomy. Herein, we report two cases of NPPE post-tracheostomy. CASE PRESENTATION: Case 1: A 69-year-old man underwent prophylactic tracheotomy for possible airway obstruction secondary to glottic carcinoma. Two hours after awakening from general anesthesia, he had difficulty expectorating and developed NPPE due to airway secretions obstructing the tracheostomy tube. Case 2: An 11-year-old boy was admitted to the intensive care unit for continuous hemodiafiltration on a ventilator under sedation. On the 76th day, the day after the tracheostomy was performed, the patient developed patient-ventilator asynchrony due to sedative withdrawal syndrome. The postulated primary mechanism was functional airway obstruction due to patient-ventilator asynchrony. CONCLUSION: These cases highlight the need to consider NPPE, even in patients with an airway secured with a tracheostomy.