The incidence of chronic otitis media with effusion (COME) after radiotherapy for nasopharyngeal or sinonasal tumors is relatively high. It is often a difficult-to-treat problem in these patients. In this retrospective study, we sought to describe the clinical course of COME in 51 patients-33 men and 18 women, aged 39 to 90 years (mean: 58.9 ± 15)-who had been referred to the Henry Ford Health System in Detroit between 2001 and 2011 for management of a tumor that had involved either the nasopharyngeal area or the sinonasal area. The median length of follow-up from the time of cancer diagnosis was 32 months. Of the 51 patients, 23 (45.1%) developed COME before, during, or after radiation therapy. Of these 23 patients, 13 (56.5%) did not experience any improvement after treatment with various combinations of therapies, including myringotomy, tympanostomy tube placement, otic drops, oral antibiotics, and corticosteroid nasal sprays. No patient- or tumor-specific factors were found to be significantly associated with the incidence of COME after irradiation to the sinonasal area. Older age and squamous cell tumor pathology were found to be significant factors for the resolution of COME after it had developed, whereas treatments with tympanostomy tubes and ear drops were not. Because of the high incidence of COME after radiotherapy and the high rate of COME's failure to resolve after tympanostomy tube insertion, we suggest that these patients require an alternative treatment.