Introduction: An enlarged tongue (macroglossia) has been reported in advanced-stage patients with amyotrophic lateral sclerosis (ALS). Methods: In this study we examined the prevalence of macroglossia and analyzed clinical correlations in 65 ALS patients on tracheostomy-invasive ventilation (TIV). Results: Macroglossia was found in 22 patients (33.8%). Compared with those without macroglossia, patients with macroglossia had a younger age of onset, longer duration of disease and TIV use, lower ALS Functional Rating Scale score, higher body mass index, lower energy intake, more severe communication impairment, and lower oral function. Logistic multivariate analysis showed that body mass index (BMI; P=0.007) and communication impairment (P=0.029) were significantly correlated with macroglossia. The duration of TIV use was at the cut-off level of significance (P=0.05). Conclusions: Macroglossia may be the result of overfeeding and replacement by fat during long-term TIV use in patients with advanced ALS. Muscle Nerve, 2016 Muscle Nerve54: 386-390, 2016