OBJECTIVE: The aim of this study was to compare the cost-effectiveness of a fixed topical combination of ciprofloxacin and hydrocortison (CH) with a fixed topical combination of polymixin neomycin and hydrocortison (PNH) in the treatment of acute otitis externa (AOE), in France. METHODS: Two randomised controlled clinical trials were conducted comparing the clinical failure rate of ciprofloxacin alone with CH and PNH: one in Europe (682 patients of whom 242 were French) and the other in the USA (728 patients). The resource utilisation and cost of clinical failure were estimated from a French panel of ENT specialists and GPs. A model was constructed to simulate the current management of PNH and CH in France. Sensitivity analyses were conducted using estimates from each studies and from the pooled analysis. Two perspectives were considered: societal and third party payer. RESULTS: The probability to have a bacterial failure was 2.4 lower (pooled analysis; P<0.0001) in the ciprofloxacin-treated patients whose infection was documented with Pseudomonas Aeruginosa (2/3 of species). The clinical failure rate was 1.9 lower (pooled analysis; P<0.05) in the same patients while no difference was found on the other species. Second line therapy included a bacteriological sample (21%), an oral antibiotic (92%) and an anti-inflammatory agent (50%), at a mean cost of 107 €. Clinical failure rate estimated by the model was 6.6% with CH and 9.3% with PNH. The incremental cost of CH over PNH, due to its better efficacy, was 5.25 € according to the third party payer perspective and 7.20 € according to the society. CONCLUSION: Because ciprofloxacin is more effective on Pseudomonas Aeruginosa , the most often encountered species in AOE, a fixed combination of ciprofloxacin and hydrocortisone allows to reduce the clinical failure rate and its cost, in comparison to PNH.