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Objective: To assess whether antimicrobial therapy in young children with acute otitis media reduces time to resolution of symptoms, overall symptom burden, and persistence of otoscopic evidence of infection. We used a cost-utility model to evaluate whether immediate antimicrobial treatment seems to be worthwhile, and if so, which antimicrobial agent is most cost effective., Study Design: We compared the cost per quality-adjusted life-day of 5 treatment regimens in children younger than 2 years of age with acute otitis media: immediate amoxicillin/clavulanate, immediate amoxicillin, immediate cefdinir, watchful waiting, and delayed prescription (DP) for antibiotic., Results: The 5 treatment regimens, listed in order from least effective to most effective were DP, watchful waiting, immediate cefdinir, immediate amoxicillin, and immediate amoxicillin/clavulanate. Listed in order from least costly to most costly, the regimens were DP, immediate amoxicillin, watchful waiting, immediate amoxicillin/clavulanate, and immediate cefdinir. The incremental cost-utility ratio of immediate amoxicillin compared with DP was $101.07 per quality-adjusted life-day gained. The incremental cost-utility ratio of immediate amoxicillin/clavulanate compared with amoxicillin was $2331.28 per quality-adjusted life-day gained., Conclusions: In children younger than 2 years of age with acute otitis media and no recent antibiotic exposure, immediate amoxicillin seems to be the most cost-effective initial treatment., (Copyright © 2017 Elsevier Inc. All rights reserved.)