OBJECTIVES: Blood stem cell mobilization, which is important as a source of hematopoietic stem cells for transplantation, is performed using granulocyte colony-stimulating factor (G-CSF), but is ineffective in around 20% of so called poor mobilizers. Combining G-CSF with plerixafor increases the percentage of successful mobilizations. The drug has orphan drug status and is approved for lymphoma and multiple myeloma patients. The objective was to compare the cost-effectiveness of three available mobilization schemes: i) the use of plerixafor “on demand” (POD) even during a first mobilization attempt in all patients who show inadequate response, ii) the standard use of Plerixafor strictly within a standard re-mobilization scheme following failure of the first mobilization (SSP), and iii) the standard (re)mobilization scheme without Plerixafor (SSNP). METHODS: Decision tree models were built to compare clinical outcomes and direct costs from the payer’s perspective in all three strategies. They were populated with efficacy resource use data from a first-of-a-kind patient registry of all patients with plerixafor administered (n=93) in 6 Czech centres. RESULTS: The success rates and costs for POD, SSP and SSNP were 94.9% and EUR 5,736 , 94.7% and EUR 6,416, and 84.7% and EUR 4,775, respectively. The direct cost per successfully treated average patient was EUR 6,046, EUR 6,776 and EUR 5,641, respectively. The cost of the first mobilization attempt with G-CSF was EUR 3,905 per patient. The cost of re-mobilization of a poor mobilizer was EUR 4,629 with G-CSF only and EUR 13,354 if plerixafor was added. The total cost of plerixafor used on-demand in the sub-cohort of poor mobilisers was EUR 13,645. CONCLUSIONS: Plerixafor substantially increases chances of success and its use is more cost-effective “on demand” during early mobilization than in subsequent re-mobilization.