Abstract Background:Acute otitis media (AOM) is the most common affliction necessitating antibiotic as the initial therapy in children. Many studies are trying to find the most effective drug with least side effects and most compliance. In this study, the efficacy of single-dose Azithromycin was considered. Methods:87 patients with AOM (based on history, otoscopic examination, and audiogram) visiting Al-Zahra and Kashani hospitals underwent 3mg/kg of azithromycin as an oral single-dose. Patients were visited 48 hr later for evaluating the failure of treatment and then, 12-16 days later for evaluating the complete or relative response to antibiotic. In 2nd visit, the audiogram was taken again. Data was analyzed with χ2 test and P < 0.05 considered statistically significant. Findings:54 (62.1%) patients were males and 33 (37.9%) were females. 72 patients were treated successfully with single-dose of azithromycin and the remainder were treated with co-Amoxiclave, 90 mg/kg, for 10 days. One patient needed myringotomy. No significant side effect was noted in patients treated with azithromycin. Conclusion:Single-dose azithromycin is an effective treatment for AOM, without any significant side effect, which is tolerated very well. Key words:Azithromycin, Acute Otitis Media, Single-Dose.