OBJECTIVES: To evaluate the costs and clinical outcomes of rituximab (R) added to first line chemotherapy vs. chemotherapy in patients with chronic lymphocytic leukemia (CLL) in Poland. METHODS: A three health state transition model was developed to evaluate the cost-effectiveness of treating patients with either chemotherapy (fludarabine +cyclophosphamide; FC) or R + FC. Patient level data were obtained from the pivotal study CLL-8 (Hallek et al., 2008). As chlorambucil (C) is frequently used in Poland, an indirect comparison of R-FC vs. C was included (patient data were obtained from the CLL-4 study, Catovsky et al. 2007). Patients commenced in the progression-free (PFS) state with transitions to progressive disease or death. PFS and overall survival (OS) data were extrapolated over 15 years with monthly cycles. Utility values originated from Hancock et. al., 2002 study. The perspective was the Public Payer. Direct costs were obtained from 4 reference oncology centers and derived from the National Health Fund. Effects and costs (PLN) were discounted at 3.5% and 5% p.a. respectively (Polish HTA guidelines). RESULTS: R-FC was more effective than FC or C. R-FC treatment resulted in 0.92 life years gained (LYG) and 0.79 quality–adjusted life years (QALY) vs. FC. Total mean costs per patient were higher for R-FC vs. FC, however the incremental cost-effectiveness ratios (ICERs) were 70,145 PLN/LYG and 81,730 PLN/QALY. The LYG and QALY gains for R-FC vs. chlorambucil were 1.87 and 1.63 leading to ICERs of 47,007 PLN/LYG and 53,826 PLN/QALY, respectively. Results were most sensitive to discounting rates changes and the time horizon. Nevertheless, in all scenarios R-FC treatment remained cost-effective. CONCLUSIONS: R-FC substantially improves patients outcomes and is an economically effective 1st line treatment for CLL patients when compared to FC or chlorambucil.