OBJECTIVES: To estimate the cost-effectiveness of G-CSF PP strategies versus pegfilgrastim SP and G-CSF SP strategies versus no prophylaxis for decreasing FN incidence in patients treated with cytotoxic chemotherapy for stages 2 and 3 breast cancer. METHODS: A Markov model was designed to track health outcomes (FN events) and medical direct costs (G-CSF, administration and FN episode costs, calculated with French Sickness Fund perspective). The model compared 9 prophylaxis strategies for three frequent BC chemotherapies (TAC [docetaxel, doxorubicin, cyclophosphamide], TC [docetaxel, cyclophosphamide] and AC-T [doxorubicin, cyclophosphamide—docetaxel]): pegfilgrastim (Neulasta®), 6-day filgrastim (Neupogen®), 11-day filgrastim, 6-day lenograstim, as either PP (initiated from first cycle) or SP (initiated after FN event), or no prophylaxis.  Inputs included transition probabilities (relative FN risks depending on the chemotherapy, determined from expert opinion and published studies: TAC, 25%; TC, 10% and AC-T 7% for AC and 21% for T), FN history and chemotherapy cycle), as well as unit costs for prophylaxis resources and overall cost associated with FN. Incremental cost-effectiveness ratios (ICERs) were expressed per FN event avoided. PP strategies were compared to SP with pegfilgrastim and SP strategies were compared to no prophylaxis. RESULTS: In the high risk population (chemotherapy FN risk ≥20%), PP-pegfilgrastim was the most cost-effective PP-G-CSF versus SP-pegfilgrastim. With TAC, ICER was €8,383 per FN avoided. In less cytotoxic regimens without considering patient risk factors, after an FN event, SP-pegfilgrastim was the most cost-effective SP-G-CSF compared to no prophylaxis, with ICERS ranging from €4614 with TC to €4795 with AC-T. CONCLUSIONS: According to our model based on French cost data, pegfilgrastim in PP and SP is more cost-effective than PP and SP with filgrastim and lenograstim in BC. PP-pegfilgrastim is the most cost-effective PP strategy in case of high risk of FN.