OBJECTIVES: Otorrhea is a common complication of acute otitis media in patients with tympanostomy tubes. The goal of this research was to determine the cost-effectiveness of ciprofloxacin 0.3%/dexamethasone 0.1% (CD) combination otic suspension relative to ofloxacin 0.3% otic solution (OFX) for the treatment of otorrhea. METHODS: A decision-analytic model emulated the ototopical treatment of otorrhea in patients with tympanostomy tubes. The economic outcome was the cost per otorrhea free day (OFD) achieved per episode of care. A clinical algorithm was developed which used three tiers of antimicrobial otorrhea therapy. Each successive tier of the model represented the re-treatment of clinical failures from the preceding tier. First tier therapy compared CD & OFX and used outcome measures taken from a randomized clinical trial (n = 599). Second tier therapy modeled the use of amoxicillin and clavulanic acid (ACA) with the outcome measures taken from the medical literature. Third tier therapy was modeled as being pathogen specific and could follow one of three separate pathways: 1) intramuscular ceftriaxone; 2) oral fluconazole; and 3) hospitalization and administration of intravenous antibiotics. Third tier outcomes were based on expert opinion. All patients were considered cured upon completion of the clinical algorithm. Cost information was taken from reference sources and presented from a payer perspective. The model timeline was 31 days. RESULTS: The estimated cost of otorrhea therapy was $237.70 for the CD pathway and $255.60 for the OFX pathway. The estimated number of OFDs per episode of care was 25.4 for the CD pathway and 23.0 for the OFX pathway. The cost-effectiveness ratios for CD and OFX therapies were $9 and $11 respectively. CONCLUSIONS: CD was both more effective and less costly than OFX for the treatment of otorrhea in patients with tympanostomy tubes. Therefore, CD was the dominant treatment between the two ototopical alternatives.