OBJECTIVES: Primary (first and subsequent cycles) prophylaxis with colony stimulating factors is recommended in the 2006 ASCO and EORTC clinical guidelines when the risk of febrile neutropenia (FN) is ≥20%. In clinical practice filgrastim has often been used for fewer than the recommended 11 days, which has been shown to compromise clinical outcomes. This study has evaluated, from an Italian perspective the cost-effectiveness of pegfilgrastim vs. filgrastim (11- or 6-days) primary prophylaxis in breast cancer patients receiving chemotherapy with ≥20% FN risk. METHODS: We constructed a decision-analytic model from a payer's perspective. Direct costs were taken from official price lists or literature data; they included: drugs, drug administration, FN-related hospitalizations and subsequent medical charges. FN risk (varied by days of filgrastim), FN case-fatality, relative dose intensity (RDI) of chemotherapy, its impact on survival, and utility scores were based on a comprehensive literature review and expert panel validation. Breast cancer mortality and all-cause deaths were obtained from official statistics. Model robustness was tested using multi-way sensitivity analyses. RESULTS: Pegfilgrastim appeared to be more effective and less expensive than 11- and 6-day filgrastim. The average cost, risk of FN (%), life expectancy and quality-adjusted life year (QALY) per person for pegfilgrastim, 11-day filgrastim, and 6-day filgrastim were €3316, 7%, 16.47 years, and 15.32 QALY; €5240, 12.5%, 16.41 years, and 15.27 QALY and €3630, 17.5%, 16.35 years, and 15.22 QALY, respectively. The results were sensitive to the relative costs of drugs and FN risk. Age and cancer stage had minimal impact. CONCLUSIONS: These preliminary data confirm that primary prophylaxis with pegfilgrastim may improve health outcomes and suggest that, in Italy, it could be cost-saving when compared with filgrastim (also for less than 11 days). A larger application of the sensitivity analyses will be necessary to further validate the model.