OBJECTIVES: To assess the direct hospital cost of Crohn's Disease (CD) in daily clinical practice in Spain. METHODS: Descriptive, naturalistic, retrospective, multicenter study of moderate/severe CD patients. Pooled data from ten hospitals, each including ten outpatients, were analysed. Clinical records were reviewed for patient demographics, disease characteristics and use of resources. A Markov model analysis was used to estimate the total cost per patient by disease severity state. The study evaluated direct medical costs in 2007 from a Spanish NHS perspective. The time horizon was a 3-year period. A sensitivity analysis was performed to assess the impact of variables on the direct medical costs of CD. RESULTS: A total of 178 patients (median age 37 (11) years; median time since diagnosis 9 (5) years) were included. Disease location was ileocecal in 47.7%, ileal in 32% and colonic in 19.7%. The most frequent symptom pattern was inflammatory (51.1%) and 39.3% presented perianal disease. The total annual cost per patient was €7722.66. Hospital admissions accounted for 57% of the total costs. The costs associated with drug treatment were 33% which are divided in 27% for biological therapies and 6% for conventional therapies. Other costs including visits, tests and surgical interventions accounted for 10%. The course of the disease showed a decline in remission/mild states and an increase in severe states being the average cost per patient and cycle of €228.578 and €2481.18 respectively. The probability of receiving a biological therapy was the only variable with a significant impact in the total cost of CD management. CONCLUSIONS: The direct cost of CD management is due mostly to hospital admissions and to the intense use of resources in the most severe disease status. The introduction of new therapies that allow a significant improvement in the evolution of patients’ disease could provide relevant economic savings for the Spanish NHS.