OBJECTIVES: Cystic fibrosis (CF) is an inherited disease that leads to progressive damage to the respiratory system, the digestive system, and other organs. Medical care utilization for patients with CF can be substantial. Recent studies of privately insured patients with CF in the US have been fairly consistent in their estimates of annual costs for the average or median patient with CF. However, the variation in cost is considerable and those patients in the tail of the distribution are also those with the most severe disease. METHODS: A national employer based claims database for the years 2004 to 2008 was used to identify patients with a valid CF diagnosis using multiple criteria. There were a total of 5019 unique patients with CF who had at least 1 year of continuous enrollment in the health plan. Annual all cause costs were calculated in total and by different settings and type of cost. The distribution of total costs was examined and the top 2.5 percentile (111 patients) were identified as high cost users.  RESULTS: While the average annual cost was approximately $50,000 for patients in our data, the average for the high cost users was over tenfold higher and ranged between $270,000 and $3.1 million. The vast majority of these costs were for inpatient stays with the average number of days spent in the hospital of 87 days. CONCLUSIONS: In this study we used a US administrative claims database to take a closer look at the most resource intensive patients with CF. A greater understanding of this group can help inform stakeholders of the level of expenses to be incurred in the treatment of severe illness and aid in cost-analysis of treatments.