To document the prevalence of adult-onset otitis media with effusion (OME), and to determine its causes, diagnostic approach, and therapeutic management. A prospective study of 167 consecutive patients with adult-onset OME. Endoscopic examination of intranasal and nasopharyngeal structures with special attention to the eustachian tube orifices was performed in all patients. In 65 patients computed tomography of the skull base, neck, and paranasal sinuses was also performed. Paranasal sinus disease, predominantly of the ethmoid system, was found to be the dominant causal factor in 110 patients (66%). Smoking-induced nasopharyngeal lymphoid hyperplasia and adult-onset adenoidal hypertrophy, two entities herein described, were the cause of OME in 15 patients (19%). Various other causes were found in 31 patients. Head and neck tumors, mainly nasopharyngeal carcinomas, were found in only eight patients (4.8%). The cause of adult-onset OME could not be determined in three patients (1.8%). Contrary to common belief, adult-onset OME is not an uncommon disease. Nasendoscopy is the mainstay of diagnostic evaluation in most patients. Computed tomography is also an important tool in most selected cases. Appropriate treatment of sinusitis resulted in resolution of OME in most patients. Sinusitis is the most common causal factor of adult-onset OME, but nasopharyngeal and parapharyngeal space-occupying lesions should be ruled out in all cases.