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Acute Otitis Media (AOM), a viral or bacterial infection of the ear, is the most common childhood infection for which antibiotics are prescribed in the United States. In 2001, the Southern California Evidence-based Practice Center conducted a systematic review of the evidence comparing treatments of AOM.This review updates the 2001 review findings on diagnosis and treatment of uncomplicated AOM, assesses the evidence for treatment of recurrent AOM, and assesses the impact of the heptavalent pneumococcal conjugate (PCV7) vaccine on the microbiology of AOM.Searches of PubMed® and the Cochrane databases were conducted from January 1998 to July 2010 using the same search strategies used for the 2001 report, with the addition of terms not considered in the 2001 review. The Web of Science was also searched for citations of the 2001 report and its peer-reviewed publications.After review by two investigators against pre-determined inclusion/exclusion criteria, we included existing systematic reviews and randomized controlled clinical trials for assessment of treatment efficacy and safety. Pooled analysis was performed for comparisons with three or more trials.Few studies were found that examined the accuracy and precision of the diagnosis of AOM. Since PCV7's introduction, AOM microbiology has shifted significantly, with Streptococcus pneumoniae becoming less prevalent and Haemophilus influenzae (HF) increasing in importance. For uncomplicated AOM, pooled analysis indicates that nine children (95% CI: 6, 20) would need to be treated with ampicillin or amoxicillin rather than placebo to note a difference in the rate of clinical success. However, in four studies of delayed treatment approaches for uncomplicated AOM, two had higher rates of clinical success with immediate antibiotic therapy while two did not, and in three studies, a marked decrease in antibiotic utilization was noted. We are unable to draw definitive conclusions regarding the comparative effectiveness of different antibiotics for AOM in children with recurrent otitis media (ROM). For ROM, long-term antibiotic administration will decrease AOM episodes from 3 to 1.5 for every 12 months of treatment per otitis prone child during active treatment (95% CI: 1.2, 2.1); however, potential consequences of long-term treatment need to be considered. Data were insufficient to draw conclusions about comparative effectiveness of different treatment strategies in subgroups of children with uncomplicated AOM. Adverse events were generally more frequent for amoxicillin-clavulanate than for cefdinir, ceftriaxone, or azithromycin. Higher quality studies and improved reporting of study characteristics related to quality are needed to provide definitive conclusions for AOM and ROM treatment options.