BackgroundUnderstanding the impacts of Head and neck radiotherapy (HNRT) on upper aerodigestive tract will promote airway safety in head-and-neck cancer population. MethodsIn this retrospective data analysis, the data of 399 HNC patients who underwent endotracheal intubation for surgery were categorized into study (HNRT, n = 133) and control group (non-HNRT, n = 266). Baseline characteristics (Age, sex, BMI,) and the factors for airway management such as neck circumference, range of motion, thyromental distance, tumor stage, number of surgeries were retrospectively analyzed. Outcome variables were stratified as primary (difficulty of mask ventilation and intubation); and secondary (Mallampatti classification, Cormack-Lehane scores (Laryngoscopy view), insertion attempts, primary intubation technique, and secondary intubation technique after a failed attempt. Chi-squared or Fisher's exact test were used for categorical association, while Wilcoxon's rank sum test was used for continuous variables. Results133 patients, who received HNRT before surgery were successfully matched to 266 non-HNRT patients with the matching factors of age, sex, and body mass index. Patients who received HNRT more likely had thyromental distance <3 finger breadths (25.6% vs 4.1%); limited neck range of motion (36.0% vs 13.2%) and Mallampatti scores of 3 and 4 (71.4% vs 41.2%), compared to controls (p < 0.001). Patients who received HNRT showed a higher likelihood of difficult intubation (95% CI: 2.47 (1.86–3.07); p ≤0.001), difficult mask ventilation (95% CI: 0.82(0.23–1.40); p = 0.006) than those who did not have HNRT. There were no significant differences between the two groups regarding laryngoscopy view, number of insertion attempts, or failed primary intubation. ConclusionHNRT changes the anatomy of upper aerodigestive tract and increases the challenge in airway management.