OBJECTIVES: To conduct a cost-effectiveness analysis of primary and secondary prophylaxis (PP & SP) with long acting granulocyte colony-stimulating factors (G-CSFs), such as pegfilgrastim, lipegfilgrastim, and short acting G-CSFs (i.e. filgrastim or lenograstim used in a 6-day regimen) for chemotherapy-induced febrile neutropenia (FN) in patients with non-Hodgkin’s Lymphoma (NHL) in Greece.   METHODS: An economic model that comprises a decision tree and a Markov chain, consisting of two phases, was locally adapted to reflect outcomes from payer perspective. The analysis was conducted for a lifetime horizon, across two different chemotherapy schemes (CHOP and CHOP-R). Clinical inputs included baseline FN risks, efficacy of G-CSFs, mortality, effects of FN on relative dose intensity, as well as direct medical costs for drug acquisition and administration and FN management. Input values were extracted from published studies while those for costs (2015 EUD) were obtained from local resources. Model outcomes were FN events avoided, and treatment strategies were compared by calculating incremental cost-effectiveness ratios (ICERs) per FN event avoided.   RESULTS: PP with pegfilgrastim provided greater health benefits in terms of FN events (calculated by combining FN risk with the efficacy of G-CSFs: 0.164) followed by PP with lipegfilgrastim (0.243) and SP with pegfilgrastim (0.522). PP with pegfilgrastim was cost-effective versus SP with pegfilgrastim across all chemotherapy schemes (ICERs of €7,490 for CHOP and € 7,781 for CHOP-R). SP with pegfilgrastim was cost-effective compared to SP with filgrastim (ICERs of €1,657 for CHOP and €1,836 for CHOP-R). SP with filgrastim was cost-effective compared to no prophylaxis (ICERs of €1,404 for CHOP and €1,585 for CHOP-R). The rest of the alternatives were dominated by a less expensive and more effective strategy.   CONCLUSIONS: Our analysis finds PP with pegfilgrastim to be a cost-effective option for chemotherapy-induced FN in NHL patients in Greece.