OBJECTIVES: Biological drugs, which are used for the treatment of severe rheumatoid arthritis (RA), have high unit costs. This has caused attention to the choice between the available biological drugs at Danish hospitals. The official list unit costs can be misleading if clinically indicated dose escalation or treatment breaks affect the total consumption of the drug. The purpose of this study was to compare the actual costs of treatment of RA with the three most commonly used biological drugs (infliximab, etanercept and adalimumab) at Danish hospitals. METHODS: The study is a cost-minimization analysis designed as a retrospective cohort study using data from medical records (n=198). Data was collected at three Danish hospitals. Consumption of biological drugs was measured during a 12 months period. Regression analysis was used to analyze the influence from patient characteristics on the dosage of infliximab. Breaks in the treatment with etanercept and adalimumab were measured from pharmacy records at one hospital. RESULTS: The average annual costs of infliximab vary due to dose escalation from € 10,546 at one hospital to € 16,109 at another hospital. Regression analysis show that dose escalation of infliximab is positively associated with pain index (DAS28) and duration of therapy. The average annual costs of etanercept and adalimumab were € 13,321 (both drugs) after adjustment for treatment breaks, which accounted for 20% of the time at one hospital. CONCLUSIONS: Real-life medicine expenses for treatment of RA with infliximab, etanercept and adalimumab tend to be equal due to dose escalation of infliximab and treatment breaks with etanercept and adalimumab. Consequently, the choice of drug can be based on considerations of efficacy, safety, patient needs and the feasibility of the treatment.