The treatment of post-irradiated otitis media with effusion (OME) remains controversial. Hence the aim of this study was to understand the long-term result of management of post-irradiated OME. Eighty-five nasopharyngeal carcinoma patients with post-irradiated OME were prospectively enrolled. All were followed up with close observation and a hearing aid was advised for those with hearing loss. If patients were still bothered by aural fullness, tinnitus or hearing impairment and did not want to continue conservative treatment, tympanostomy plus aspiration was performed. Only those who had persistent OME and failed repeated tympanostomy for at least 3 months were suggested to undergo grommet insertion. After a mean follow-up of 842.1 ± 49.0 days from the completion of radiotherapy, OME was present in 45 patients (52.9%). Another 16 (18.8%) had chronic discharging ears with or without perforated eardrums. Grommets remained on the eardrums in eight patients. Among them, five were without otorrhea but discharge came from grommet tubes intermittently in three patients. Only 15 (17.6%) were free of OME, and one patient had a dry perforated eardrum. Our results showed current methods did not result in long-term resolution of some recalcitrant post-irradiated OME.