Otitis media with effusion (OME) is defined as a collection of fluid in the middle ear without signs or symptoms of acute ear infection. OME has several potential causes. The leading causes include viral upper respiratory infection, acute otitis media (AOM), and chronic dysfunction of the eustachian tube. However, other potential explanations include ciliary dysfunction, proliferation of fluid-producing goblet cells, allergy and residual bacterial antigens, and biofilm. More recent research suggests that mucoglycoproteins cause the hearing loss and much of the fluid presence that is the hallmark of OME. The presence of fluid in the middle ear decreases tympanic membrane and middle ear function, leading to decreased hearing, a "fullness" sensation in the ear, and occasionally pain from the pressure changes. OME occurs commonly during childhood, with as many as 90 percent of children (80% of individual ears) having at least one episode of OME by age 10. OME disproportionately affects some subpopulations of children. Those with cleft palate, Down syndrome, and other craniofacial anomalies are at high risk for anatomic causes of OME and compromised function of the eustachian tube. Individuals of American Indian, Alaskan, and Asian backgrounds are believed to be at greater risk, as are children with adenoid hyperplasia. In addition, children with sensorineural hearing loss will likely be more affected by the secondary conductive hearing loss that occurs with OME. Although rare, OME also occurs in adults. This usually happens after patients develop a severe upper respiratory infection such as sinusitis, severe allergies, or rapid change in air pressure after an airplane flight or a scuba dive. The incidence of prolonged OME in adults is not known, but it is much less common than in children. Despite the high prevalence of OME, its long-term impact on child developmental outcomes such as speech, language, intelligence, and hearing remains unclear. The near universality of this condition in children and the high expenditures for treating OME make this an important topic for a comparative effectiveness review. This comparative review includes all interventions currently in use for treating OME-surgical, pharmacological, and nonpharmacological; we excluded antihistamines and decongestants, which have been extensively reviewed previously and demonstrated to have no benefit in this population. Antibiotics are the subject of a recent Cochrane review, and in cooperation with our Technical Expert Panel (TEP), we decided to not duplicate their work. The intent of our review was to cover the entire range of individuals who have OME; in particular, we sought evidence specific to populations who have not been examined in past reviews such as adults and children with comorbid conditions such as Down syndrome, cleft palate, or existing hearing loss. Five Key Questions (KQs) in this review have been addressed: KQ 1. What is the comparative effectiveness of the following treatment options (active treatments and watchful waiting) in affecting clinical outcomes or health care utilization in patients with OME? Treatment options include: tympanostomy tubes, myringotomy, oral or topical nasal steroids, autoinflation, complementary and alternative medical procedures, watchful waiting, and variations in surgical technique or procedures. KQ 2. What is the comparative effectiveness of the different treatment options listed in KQ 1 (active treatments, watchful waiting, and variations in surgical procedures) in improving functional and health-related quality of life outcomes in patients with OME? KQ 3. What are the harms or tolerability among the different treatment options? KQ 4. What are the comparative benefits and harms of treatment options in subgroups of patients with OME? KQ 5. Is the comparative effectiveness of treatment options related to factors affecting health care delivery or the receipt of pneumococcal vaccine inoculation?