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Background Chronic rhinosinusitis (CRS) is an inflammatory disease that affects 2% to 16% of the US population. Despite its increasing prevalence, there are currently limited data in the literature evaluating the economic burden of this disease. Objective This study aimed to determine the direct health care costs of CRS from the perspective of the US government. Methods A prevalence-based approach was used to estimate cost of illness for CRS from the 2011 Medical Expenditure Panel Survey database by using a 4-part model:(1) an estimated sum of all health care expenditures,(2) an attribution model for disease-specific estimation of expenditures,(3) an estimation based on a propensity score model, and (4) estimated disease-specific expenditure by using a linear regression–based approach. A disease prevalence of 3.5% was used. Results The mean CRS-specific annual expenditure was $5955 (95% CI …