RATIONALE: For anticipated difficult airways, awake tracheal intubation is strongly recommended by guidelines for its high success rate and safety. The key to successful awake tracheal intubation is effective airway topicalization. Currently available topicalization techniques have corresponding drawbacks and complications. Especially for subglottic topicalization, noninvasive techniques are not effective. Subglottic spray via epidural catheter with a flexible bronchoscope provided an effective and noninvasive technique. PATIENT CONCERNS: A 73-year-old female patient with a history of giant goiter for 9 years suffered chest tightness and shortness of breath, and a 54-year-old male patient with a neck mass and hoarseness were scheduled for thyroidectomy. DIAGNOSES: Two cases of anticipated difficult airway due to compression by a giant goiter. INTERVENTIONS: The subglottic area was topicalized via an epidural catheter with a flexible bronchoscope, and awake tracheal intubation was successfully performed. OUTCOMES: This technique was effective in eliminating airway reactions and hemodynamic fluctuations during awake intubation and improving the intubation success rate and patient tolerance. LESSONS: This is the first report of subglottic topicalization via an epidural catheter with a flexible bronchoscope applied in cases of awake intubation in giant goiter. The epidural catheter spray is safe and effective in awake intubation of an anticipated difficult airway, and this noninvasive technique is an alternative option to transtracheal injection.