OBJECTIVES: Little information exists on the acute treatment provided for rhinosinusitis and its associated costs. We hypothesize that introducing the administration of mometasone furoate (MFNS) as a treatment for rhinosinusitis will have a substantial impact on medical resource costs, outcomes and possibly cost-effectiveness. The goal of this paper is to estimate the cost-effectiveness of treating patients with rhinosinusitis with MFNS versus amoxicillin. METHODS: A decision-analytic model was developed to estimate lifetime costs and outcomes associated with MFNS 200µg twice daily and amoxicillin 500mg three times daily in treating rhinosinusitis from the Mexican healthcare  perspective. This study further do not included MFNS 200µg once daily as a treatment arm because it was not found to be superior to amoxicillin. Data sources included published literature, clinical trials, official price/tariff lists, and Delphi panel data. The time horizon was 2 weeks. The effectiveness outcomes of the study were modeled as changes in the Major Symptom Score (MSS). MSS consists of five questions concerning rhinorrhoea, post-nasal drip, nasal congestion, sinus headache, and facial pain. Costs were valued in US dollar, year 2012 values. Multiple 1-way sensitivity analyses and a probabilistic sensitivity analysis using Monte Carlo simulation were performed to handle uncertainty RESULTS: The projected costs were US$ 258 with MFNS and $US 272 with. The benefits (changes in the MSS) were 0.52 with MFNS 0.45  with Amoxicilin. MFNS was associated with a cost savings per patient of US$ 14 versus amoxicillin over a period of 2 weeks from a healthcare perspective. The incremental cost-effectiveness ratio for MFNS dominated Amoxicilin. Sensitivity analysis confirmed the overall cost savings and gains in effectiveness. CONCLUSIONS: Our analysis suggests MFNS improves health outcomes in a cost-effective manner compared with Amoxicilin. The economic value of Amoxicillin is influenced by difficulties involved in diagnosing the condition, effectiveness, resistance, patient compliance with treatment, and treatment failure associated with antibiotics.