OBJECTIVES: Primary prophylaxis with granulocyte-colony stimulating factors, used in the first and subsequent cycles of chemotherapy, is recommended by the 2006 ASCO and EORTC guidelines when the overall risk of febrile neutropenia (FN) is =20%. We evaluated the cost-effectiveness of pegfilgrastim versus filgrastim used for 11 days (as used in clinical trials) and 6 days (often used in clinical practice) in patients with aggressive non-Hodgkin's lymphoma (NHL) receiving CHOP-21 chemotherapy in Italy. METHODS: A decision-analytic model was constructed from a health care payer's perspective with a life-time model horizon. Costs (2006 value) including drugs, drug administration, FN-related hospitalisations, and subsequent medical costs were acquired from official price lists or literature. FN risk, FN case-fatality, relative dose intensity (RDI), and impact of RDI on survival were based on data from a comprehensive literature review and expert panel validation. Using data from a meta-analysis and several observational studies, we estimated that the absolute risk of FN in patients receiving pegfilgrastim decreased from 19.6% to 13.1% (6.5 percentage points) versus 11-day filgrastim, and from 25.1% to 13.1% (12 percentage points) versus 6-day filgrastim. NHL mortality and all-cause mortality were from literature. Sensitivity analyses were performed on key parameters. RESULTS: Pegfilgrastim was cost saving compared with 11-day filgrastim (€5053 versus €7465). Compared with 6-day filgrastim, the incremental cost-effectiveness ratio (ICER) was €475 per FN event avoided or €5 per 1% decrease in absolute risk of FN. Pegfilgrastim achieved 0.112 more discounted life-years (LY) at a minimal cost increase of €57 (€5053 versus €4996) per person, yielding an ICER of €513/LY gained. Results were most sensitive to the relative risk of FN for filgrastim versus pegfilgrastim. CONCLUSION: In Italy, pegfilgrastim was cost saving compared with 11-day filgrastim and appeared to be cost-effective compared with filgrastim used for 6 days per cycle of CHOP-21.