OBJECTIVES:  Cystic fibrosis (CF) is a chronic lung disease occurring at a rate of 1 in 3,400 births and affecting 30,000 people in the U.S and 70,000 globally. Current understanding of the burden of CF within the health care system is lacking. The goal of the present study is to estimate the cost of illness of CF using publicly available data. METHODS:  The study is a retrospective analysis of Medical Expenditure Panel Survey (MEPS) data from 2010-2014 using ICD-9-CM diagnosis code for principal diagnosis CF (277.xx). Descriptive analyses were conducted to assess patient demographics, clinical characteristics such as comorbidities and resource utilization related to events in different settings. Cost calculations included expenditures occurring in inpatient, outpatient, office, home health and emergency visits, as well as prescription drugs utilization. Unweighted and weighted annual and cumulative out-of-pocket (OOP) costs and total health care costs were calculated. All statistical analyses were conducted using Statistical Analysis System 9.4 (SAS Institute; Cary, NC). RESULTS:  A total of 130 unique CF cases were available, of whom 109 (83.8%) reported using a CF-related medical service. The mean age of the sample was 38.2 ± 25.3 years with a mean household income of $59,903.78 ± 54,970.57. The cohort was predominantly female (n=70; 64.2%), Caucasian (n=71; 65.1%), privately insured (n=73; 67.0%) and most commonly had comorbid hypertension (n=45; 41.3%). Over 5 years, unweighted cumulative OOP costs were $31,828.58 and total health care costs were $455,539.70. Prescription medications accounted for 57.5% of OOP costs ($18,328.66) and 33% of total health care costs ($150,634.20). Using weighted data, the cumulative OOP costs was $615,098,138 and total healthcare costs was $6,691,134,764. CONCLUSIONS:  The study provides health care expenditure estimates for individuals with CF. These estimates can serve as a guide for policy makers to better determine resource utilization and cost-effectiveness of treatments in CF.