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Background: Functional endoscopic sinus surgery (FESS) is one of the most commonly performed otolaryngologic procedures and is associated with significant cost variability., Methods: We performed a retrospective analysis of all inflammatory sinus surgeries at a single tertiary care medical center from July 2021 to July 2023. The electronic medical record was reviewed for patient factors and cost variables for each procedure, and multivariable analysis was performed., Results: A total of 221 patients were included in analysis with a mean age of 48.2 years. There was a 44.8% incidence (n = 99) of nasal polyps and 31.2% (n = 69) of cases were revision surgeries. The average total cost for the surgical encounter was $8960.31 (standard deviation $1967.97). Operating room time represented $4912.46 (54.8% of all costs), while average operating room supply costs were $1296.06 (14.5%) and recovery room costs were $919.48 (10.3%). Total costs were significantly associated with length of surgery ($7.83/min, p = 0.04), in addition to presence of nasal polyps ($531.96, p = 0.04). There was no significant association between total costs and the remaining clinical and demographic factors., Conclusions: Costs associated with ambulatory FESS for inflammatory sinus disease vary across patients and this cost variability is predominantly driven by time efficiency within the operating room, as well as supply utilization and nasal polyposis to a lesser degree. As a result, operating room efficiency represents a primary target for cost-related interventions. Additionally, our data provide a framework for surgeons and hospitals to make evidence-based decisions on intraoperative equipment in a tradeoff between efficiency and supply costs. Our findings indicate that an approach focused on streamlining efficiency across the entire ambulatory surgery encounter will have the greatest impact on reducing healthcare expenses for both the patient and the health system., (© 2024 The Author(s). International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)