Background: This study was conducted to assess the comparison of azithromycin versus amoxicillin-clavulanate in the treatment of acute sinusitis in children.Materials and Methods: This study comprised 100 children in the age range of 5 to 15 years, 50 of them were boys and 50 were girls. All patients had a throat and nasal smear on culture and antibiogram, as well as a paranasal sinus X-ray and laboratory results. Azithromycin was administered in a single daily dose of 10 mg/kg for three days to patients with positive bacteriological findings in the nose and X-ray obvious sinusitis (maxillary sinus was the predominant site of inflammation). Alternatively, amoxicillin-clavulanate was administered three times a day at a dose of 45 mg/kg for ten days along with twice-daily use of ephedrine hydrochloride nasal decongestive solution. A paranasal sinus X-ray was performed and a checkup of throat and nasal smear 10–15 days after starting medication was done.Results: There were 50 male subjects and 50 female subjects. Fifty of the 100 patients received azithromycin treatment (Group 1), and the other fifty received amoxicillin/clavulanate (Group 2). There were fifty male and fifty female children among the total of 100 observed. 40 between 10-15 years old and 60 between 5-10 years old made up the age distribution. After 20 days, the therapeutic impact was visible in certain patients. It was observed that both the antibiotics were well tolerated Adverse event rates were modest in both therapy groups, and azithromycin and amoxicillin/clavulanate did not differ significantly from one another. Neither agent was responsible for any significant adverse responses that occurred.Conclusion: When treating acute sinusitis, azithromycin given once daily for three days is just as effective as amoxicillin and clavulanate given three times daily for ten days.