OBJECTIVES: Little information exists on the acute treatment provided for rhinosinusitis and its associated costs. This study assessed the cost-effectiveness of mometasone furoate versus amoxicillin for the treatment of rhinosinusitis in Mexico from a health care perspective. METHODS: A decision tree model was constructed using decision analytical techniques. Data sources included published literature, clinical trials, official price/tariff lists, and Delphi panel data. The comparators were mometasone furoate 200µg twice daily and amoxicillin 500mg three times daily. This study further do not included MFNS 200µg once daily as a treatment arm because it was not found to be superior to amoxicillin. 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. One-way and probabilistic sensitivity analyses were conducted to evaluate uncertainty in the results.  RESULTS: The projected costs were US$ 258 with Mometasone furoate and $US 272 with.The benefits were 0.52 with Mometasone furoate, 0.45 with Amoxicilin. Mometasone furoate was associated with a cost savings per patient of US$ 13.92 versus amoxicillin over a period of 2 weeks from a health care perspective. The incremental cost-effectiveness ratio for Mometasone furoate dominated Amoxicilin. Sensitivity analysis confirmed the overall cost savings and gains in effectiveness.  CONCLUSIONS: Our analysis suggests Mometasone Furoate improves health outcomes in a cost-effective manner compared with Amoxicilin, and highlights the importance of using evidence-based effectiveness estimates in economic studies of rhinosinusitis therapies