OBJECTIVES: Beneflur®, whose active principle is fludarabine, has an oral and an intravenous (i.v.) formulation. The objective of the present study was to compare the efficiency of both formulations by means of a cost-minimization analysis in the treatment of B-cell chronic lymphocytic leukaemia (CLL) in Spain. METHODS: Existence of previous clinical evidence on the therapeutic equivalence between both fludarabine formulations justified a cost-minimization analysis to compare efficiency. The National Health System (NHS) perspective was taken including only direct costs. Also indirect costs were considered allowing a societal viewpoint. Data on resources use were obtained from published literature and through an expert panel. Unit costs were obtained from Spanish costs databases. Generic i.v. fludarabine cost was used. The model was built in Microsoft Excel and a sensitivity analysis by means of two different techniques (scenario analysis and Monte-Carlo Simulation) was performed to ensure robustness of results. RESULTS: Although acquisition costs for oral fludarabine are higher than for i.v. fludarabine, higher administration costs for the i.v. formulation due to hospital administration and adverse event costs compensate them, resulting in net savings for the NHS of €2152 and €1322 using the oral formulation (baseline scenario), in monotherapy and in combined therapy respectively. The range of savings obtained through the scenario analysis was: ≥ €1024 ≤ €3280 for monotherapy and ≥ €617 ≤ €2027 for combined therapy. Indirect costs, i.e. lost productivity, charge only i.v. fludarabine, adding extra savings to the oral formulation. Monte-Carlo results confirmed model robustness. CONCLUSIONS: Oral fludarabine has equivalent efficacy and an improved safety profile than intravenous fludarabine showing total lower costs both in monotherapy and in combination with cyclophosphamide, from the perspective of the National Health System in Spain. Hence, oral fludarabine should be administered instead of intravenous fludarabine unless contra-indicated.