OBJECTIVES: To assess clinical effectiveness and costs of Augmentin ES® (amoxicillin/clavulanic acid 90/6.4 mg/kg/day in two divided doses) vs azithromycin (10mg/kg, day 1; 5mg/kg/d, days 2-5) in acute otitis media treatment in Poland from the public payer (NHF) and payer (NHF+patient) perspective. METHODS: Systematic review according to Cochrane Collaboration guidelines and clinical effectiveness analysis according to Polish HTA Guidelines were performed. Medline (Pubmed) Cochrane and EMBASE were searched (August 2006). Only RCTs with high credibility assessment (based on Jadad scale) were included in the systematic review. Overall costs of treatment were taken into account, including cost of pharmacotherapy, drug administration, second-line therapy, complications of otitis media and adverse events. Sensitivity analysis was performed according to a range of acquisition costs of Augmentin ES® and azithromycin (+/- 20%). All calculations were performed for 2006 (€1=PLN3.8). RESULTS: Randomized head-to-head clinical trial of Augmentin ES® vs azithromycin was found and significant difference in clinical cure rate between two drugs was revealed: 90.5% vs 80.9%, respectively; no significant differences in safety profile were found. Cost analysis revealed that savings per patient when Augmentin ES® is used in place of azithromycin were: PLN49 (€12.9) (public payer) and PLN38.3 PLN (€10.1) (payer). Results of clinical and cost analysis proved that azithromycin therapy is dominated by Augmentin ES®. The results proved to be robust to variations in the drugs cost acquired in sensitivity analysis. Savings accompanying clinical cure of one patient in case of Augmentin ES® used in place of azithromycin were: PLN510.5 (€134.3) (from public payer perspective) and PLN399.2 (€105) (payer perspective). CONCLUSION: Augmentin ES® compared with azithromyycin therapy brings significant savings and is a cost-effective treatment of acute otitis media in Poland.