OBJECTIVES: To evaluate the cost-effectiveness of primary prophylaxis (PP) with pegfilgrastim vs lipegfilgrastim to reduce the incidence of febrile neutropenia (FN) in patients with stage II breast cancer receiving 4-cycle TC (docetaxel, cyclophosphamide) and patients with non-Hodgkin lymphoma receiving 6-cycle R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) over a lifetime horizon from a Belgian payer perspective. METHODS: A Markov cycle tree model tracks FN events during chemotherapy (3-week cycles) and long-term survival (1-year cycles).  Model inputs include: the odds ratio of FN between lipegfilgrastim PP and pegfilgrastim PP (median [95% credible interval]: 1.39 [0.54–3.50]), estimated from a meta-analysis of randomized controlled trials using mixed-treatment comparison; equivalent prices of lipegfilgrastim and pegfilgrastim since the launch of lipegfilgrastim in Belgium (August 2014); mortality (which is affected by FN and chemotherapy relative dose intensity); costs (in 2014 €); and utilities.  All inputs were estimated from public sources, research databases, and peer-reviewed publications.  Quality-adjusted life-years (QALYs) and expected lifetime costs were estimated for each strategy.  Probabilistic sensitivity analyses (PSA) and scenario analyses were conducted. RESULTS: Pegfilgrastim PP dominated lipegfilgrastim PP, with total lifetime costs of €7,482 vs €7,806 for TC and €19,149 vs €19,801 for R-CHOP and total lifetime QALYs of 13.379 vs 13.348 for TC and 4.241 vs 4.184 for R-CHOP.  At a willingness-to-pay threshold of €30,000 per QALY, pegfilgrastim PP was cost-effective vs lipegfilgrastim PP in approximately 75% of PSA simulations for both regimens.  In a scenario analysis when the lipegfilgrastim price was set at 90% that of pegfilgrastim, the incremental cost-effectiveness ratios for pegfilgrastim PP vs lipegfilgrastim PP were €4,700 per QALY gained for TC and €857 per QALY gained for R-CHOP.    CONCLUSIONS: From a Belgian payer perspective, pegfilgrastim PP is cost-effective vs lipegfilgrastim PP in patients with stage II breast cancer receiving TC and in patients with non-Hodgkin lymphoma receiving R-CHOP.