OBJECTIVES: To assess cost-utility in Belgium of once-per-cycle primary prophylaxis (PP) with pegfilgrastim vs. no prophylaxis and vs. PP with daily granulocyte-colony stimulating factors (G-CSF) filgrastim or lenograstim (11-days per label or 6- days per common clinical practice) for reducing febrile neutropenia (FN) incidence in women with primary breast cancer receiving chemotherapy carrying a 20% or higher overall risk of FN. METHODS: A decision-analytic model was constructed from a healthcare-payer perspective. Costs were from official Belgian list prices (April 2012) or literature and included drugs, drug administration, FN-hospitalizations and FN-related medical costs. Effectiveness inputs in terms of relative risk reduction (RRR) for FN were based on the most recently published meta-analysis (Cooper 2011). Survival and utility inputs were obtained from available data for breast cancer patients in the US (Lyman 2009) and the UK (Whyte 2011). Outcomes included number needed to treat to avoid an episode of FN (NNT), and incremental cost effectiveness ratio (ICER) in terms of cost per quality-adjusted life-years (QALY). A univariate sensitivity analysis evaluated the robustness of the model. RESULTS: Pegfilgrastim demonstrated the lowest NNT (4.69). In terms of cost-utility, pegfilgrastim was dominant vs. 11-day filgrastim or lenograstim and was considered cost-effective vs. no prophylaxis (€24,675/QALY) and 6-day filgrastim (€18,265/QALY) or lenograstim (€12,782/QALY). In a scenario analysis reducing the prices of daily G-CSFs by 30%, pegfilgrastim remained cost-effective at a willingness to pay threshold of €30,000. The sensitivity analysis revealed that most sensitive variables were effectiveness (RRR), incremental utility values (LYs and QALYs) and cost of G-CSFs, and demonstrated the overall model to be robust. CONCLUSIONS: In a Belgian setting, pegfilgrastim offered the most cost-effective approach to primary prophylaxis of FN. In the cost-utility analysis pegfilgrastim primary prophylaxis was dominant vs. 11-day G-CSF primary prophylaxis and cost-effective vs. no prophylaxis and 6-day G-CSF primary prophylaxis.