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 clinical guidelines when the overall risk of febrile neutropenia (FN) is =20%. Pegfilgrastim effectively reduces the risk of FN with a single injection per cycle compared with 11 injections on average for filgrastim as observed in clinical trials. The study objective was to evaluate the cost-effectiveness of primary prophylaxis with pegfilgrastim versus filgrastim in patients with aggressive non-Hodgkin's lymphoma (NHL) receiving CHOP-21 chemotherapy in Spain. 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 medical costs subsequent to FN hospitalisations were acquired from official price lists or literature. Other model inputs including FN risk, FN case-fatality, relative dose intensity (RDI), the impact of RDI on survival, and health utilities were based on data from a comprehensive literature review and expert panel validation. Using data from a meta-analysis, 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. NHL mortality and all-cause mortality were obtained from official statistics. Sensitivity analyses were performed on key parameters. RESULTS: The incremental cost-effectiveness ratio (ICER) was €185 per FN event avoided or €2 per 1% decrease in absolute risk of FN. Pegfilgrastim achieved 0.06 more discounted life-years or 0.053 more discounted quality-adjusted life-years (QALY) at a minimal cost increase of €12 per person (€6550 versus €6538), yielding an ICER of €195/LYG and €218/QALY saved. Results were most sensitive to the relative risk of FN for 11-day filgrastim versus pegfilgrastim. CONCLUSION: In Spain, pegfilgrastim was cost-effective compared with 11-day filgrastim in NHL patients using CHOP-21.