High-frequency jet ventilation has been reported as an effective method of ventilation during laryngoscopy, but may expose the patient to the risks of barotrauma or alveolar hypoventilation. The aim of the study was to evaluate the determining factors of pulmonary complications under high-frequency jet ventilation in 83 patients undergoing laryngoscopy for upper airway cancer. Pulmonary distention was mainly influenced by upper airway obstruction score (p = .0001), while patients with chronic obstructive pulmonary disease (COPD) did not suffer from gas trapping. Impaired gas exchange was predicted by increased weight (p = .0001), smaller injector diameter (p = .02), and lower airway obstruction (p = .001). Hypercapnia occurred in both upper and lower airway obstruction, while hypoxemia was principally observed in COPD patients. Emphasis is placed on monitoring by pulse oximetry, end-expiratory pressure, and PCO2 measurement, especially in patients with obesity, COPD, or upper airway obstruction.