Epiglottic cysts is a rare but potentially lethal supraglottic airway pathology in infants due to the high risk of cannot intubation or cannot ventilation. Awake fiberoptic intubation appeared to be the safest technique, but it is very challenging in infants with large epiglottic cysts. Even it has the risk of airway loss. We report that cyst aspiration is an effective treatment as the first-choice procedure for airway management in an infant with large epiglottic cysts.A 46-day-old male infant weighing 2.3 kg presented to the emergency room with difficulty feeding, worsening stridor, and progressive respiratory distress. Epiglottic cysts was diagnosed, but fibro bronchoscopy examination failed, as the fiberoptic bronchoscope was unable to cross the epiglottic cysts to the trachea. The infant was transferred to the operating room for emergency cystectomy under general anesthesia. Spontaneous respiration was maintained during anesthesia induction, and cyst aspiration was performed as the first procedure for airway management under video laryngoscopy considering that the preoperative fibro bronchoscopy examination failed. Then, the endotracheal tube was intubated successfully. Cystectomy was performed uneventfully, and the infant was safely transferred to the intensive care unit after surgery. The infant was extubated smoothly on the third postoperative day and discharged on the eighth day after surgery. On follow-up 1 year after the surgery, a normal airway was found by fibro bronchoscopy examination.Epiglottic cyst aspiration can be considered the first procedure for airway management in infants with large epiglottic cysts.©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.