Background: Mucopolysaccharidoses (MPSs) are lysosomal storage disorders in which glycosaminoglycans accumulate due to insufficiency of the enzymes to degrade them. Patients have organomegaly, short stature, and/or intellectual disability. The earliest symptoms are otologic and upper respiratory obstruction and are the main reasons for doctor consultation. Methods: We reviewed 42 patients (30 male and 12 female), with a median age of 20.5 years, who had MPS (16.7% type I, 35.7% type II, 19.0% type IIIB, 21.4% type IVA, and 7.2% type VI). Otorhinolaryngologic manifestations were collected, and quality of life after surgery was documented. Results: Ear, nose, and throat (ENT) symptoms occurred in patients with all MPS types. We found recurrent otitis media in 42.9% of cases. We noted hearing loss in 81.0% (mixed in 45.2%, conductive in 19.0%, sensorineural in 16.7%), adenotonsillar hypertrophy in 76.2%, frequent infections of the upper airway in 47.6%, and obstructive sleep apnea syndrome in 26.2%. Seventy-six percent of patients underwent ENT surgery, including adenoidectomy, tonsillectomy, tympanostomy with ventilation tube insertion, tracheotomy, and supraglottoplasty. Conclusions: ENT surgery reduced the severity of hearing loss, and decreased the degree of symptoms related to upper airway obstruction which improved patients’ quality of life.