OBJECTIVES: To estimate from a health service perspective the impact of rational use (RU) of high costing chemotherapy agents (HCCA). METHODS: A discussion forum with specialists was performed to optimize use of chemotherapy without compromising patient prognosis within a tertiary cancer hospital. A consensus was reached within the clinical oncology staff that restricted use of 2 drug candidates from the top 15 HCCA would not be harmful to patient outcomes based on literature data. These 15 drugs were responsible for 75% of overall chemotherapy purchase cost. Gemcitabine was used predominantly for 2nd line treatment of advanced breast cancer (BC) and 1st line treatment of pancreas and bladder cancer. Epirubicin was mainly used in adjuvant and palliative treatment of BC. Prescription of chemotherapy was based on medical claims data from outpatient drug administration between January 2005 and December 2005. Medication costs were based on average wholesale price for each drug. Substitution of epirubicin by doxorubicin for the treatment of the majority of BC patients, and the substitution of gemcitabine by other agents with equivalent response rates for 2nd line treatment of advanced BC was implemented in Janaury 2006. RESULTS: Together these two drugs represented 15% of chemotherapy direct cost in 2005. RU of these HCCA was responsible for 56% decline in median prescription of gemcitabine per month (177.000 mg before RU versus 78.000 mg after RU; p=0,035). Similarly, median prescription of epirubicin was reduced 81% per month (148,000 mg before RU versus 28,000 mg after RU; p=0.013) from 2005 to 2006. This represented a cost saving strategy of 4% in the overall budget of chemotherapy purchase (annual budget US$ 6.45 M in 2006). CONCLUSION: The RU of HCCA drugs reduced the direct cost of chemotherapy unit and allow us a better resource distribution.