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Patients with acromegaly have a high risk of difficult laryngoscopy. However, clinical predictors, such as upper lip bite test or modified Mallampati class, show limited predictive performance for difficult laryngoscopy in such patients. In this retrospective study, we evaluated radiographic indices obtained from skull lateral x-ray and ostiomeatal unit computed tomography images to predict difficult laryngoscopy in acromegaly patients.Data on demographics, preoperative serum levels of pituitary hormones, and radiographic indices were collected from 90 acromegaly patients that underwent transsphenoidal removal for pituitary tumor from January 2010 to December 2016. Difficult laryngoscopy was defined as Cormack-Lehane grade ≥III.Difficult laryngoscopy occurred in 21 (23%) patients. In univariate analysis, age and radiographic indices indicating tongue size, such as tongue area (TA) on ostiomeatal unit computed tomography, linear distance from the alveolar line of the mandible to the hyoid bone, and linear distance from the interior border of the mandible to the hyoid bone on skull lateral x-ray, were associated with difficult laryngoscopy. In multivariate analysis, age (odds ratio [95% confidence interval], 1.084 [1.037-1.190]; P=0.002) and TA (1.002 [1.000-1.003], P=0.014) were independent risk factors for difficult laryngoscopy. The area under the curve of the combined model of age and TA was 0.80.Old age and radiographic predictors indicating large tongue size (large TA, long alveolar line of the mandible to the hyoid bone and mandible to the hyoid bone) were associated with an increased rate of difficult laryngoscopy in acromegaly patients. Preoperative radiographic measurements of tongue size can be helpful for safe airway management in such patients.