OBJECTIVES: Cystic fibrosis (CF) a common life-limiting autosomal recessive condition. Aside from respiratory complications the degenerative nature of CF is a causal factor for many other complicating conditions both acute and chronic. The objective of this study is to examine the impact of comorbid conditions on hospitalized CF patients. METHODS: A retrospective descriptive study was conducted on CF patients hospitalized in the MedAssets health system data from October 2015 through September 2016. Multivariable regression was used to identify complicating conditions that are significant drivers of inpatient admission, length of stay (LOS), and hospitalization cost. RESULTS: The sample included 7,936 unique patients from 298 hospitals. Half of the population was female (54.0%) with an average age of 22.4 years, and average Charlson comorbidity score of 1.4. The patient population averaged 3.7 outpatient visits during the study period. Over 29% of patients were admitted as an inpatient with an average LOS of 10.4 days and an average cost of $25,749. The population averaged nearly three comorbidities which primarily fell into respiratory (64.3%), gastrointestinal (41.6%), cardiovascular (30.4%) anxiety/depression (19.6%) disease groups. Primary predictors of inpatient admission included malnutrition (OR 5.5, 95% CL 4.8 - 6.3), chronic lower respiratory disease (OR 3.4, CL 3.3 - 3.8), epilepsy (OR 4.3, CL 3.0 - 6.1), and anemia (OR 4.2, CL 3.6 - 5.0). Once admitted respiratory failure (RR 1.6, CL 1.5 - 1.7), malnutrition (RR 1.4, CL 1.3 - 1.4), and arrhythmias (RR 1.2, CL 1.1 - 1.4) contributed to longer LOS. Additionally, coagulation defects (RR 1.2, CL 1.1 - 1.3), and coronary artery disease (RR 1.5, CL, 1.3 - 1.9) contributed to higher cost. CONCLUSIONS: Cystic fibrosis patients admitted to the hospital have a large number of comorbidities and complications. Improvements in disease management may lead to better patient outcomes and a reduction in hospital utilization and healthcare costs.