Background: Otitis media is an ear infection middle that caused by bacteria or a viruses, whichrnaffects more children. Amoxicillin/clavulanate is the drug of choice for otitis media currently.rnHowever emergency of resistance, long duration of treatment and more adverse reactions makernamoxicillin to be a less valuable choice for treating otitis media. rnObjective: The aim of this study is to compare the efficacy and safety of azithromycin againstrnamoxicillin/clavulanate for the treatment of otitis media in children. rnMethodology: Two databases PubMed and Cochrane library were searched systematically andrnfrom Google scholar manually searched. The articles were screened by two review authors,rnduplicates were removed by Mendeley reference manager software. Remained search results wasrnscreened for fulfillment of PICOs and inclusion criteria. Articles which did not fulfill the PICOrnand inclusion criteria were excluded from the study. Data extracted by the first review author andrnchecked by second author. For analysis, all the included studies for review are provide on a tablernwith relevant findings. Meta-analysis was performed using STATA software version 16, andrnMantel-Haenszel method and effect measure odds ratio was employed for data analysis, datarnsynthesis and creating forest plot. rnResult: Seven hundred fifty one records were identified and fourteen studies have fulfilled therninclusion criteria. In twelve studies azithromycin had equivalent clinical efficacy and in the rnremaining two studies the bacteriologic efficacy of azithromycin is lower thanrnamoxicillin/clavulante. Meta-analysis results showed a small statistical difference on efficacy inrnfavor of amoxicillin/clavulanate after completion of treatment and there was no statisticalrnsignificant difference on efficacy on follow up. There was statistically significant difference ofrnclinical adverse events more in amoxicillin/clavulanate group than in azithromycin. rnConclusion: Efficacy of azithromycin is not inferior to amoxicillin/clavulanate to treat otitisrnmedia in children, and it is more safe and tolerable in children than amoxicillin/clavulanate. rnRecommendations: Azithromycin can be a possible first line treatment option of otitis media.rnMore up to date well controlled clinical trial researches are required to replacernamoxicillin/clavuluanate.