Peripheral blood stem cells (PBSCs) are preferred source of hematopoietic stem cells for autologous transplantation. Mobilization of PBSCs using chemotherapy and/or granulocyte colony-stimulating factor (G-CSF) however fails in around 20%. Combining G-CSF with plerixafor increases the mobilizations success. We compared cost-effectiveness of following schemes: the use of plerixafor “on demand” (POD) during the first mobilization in all patients with inadequate response, the remobilization with plerixafor following failure of the first standard mobilization (SSP), and the standard (re)mobilization scheme without plerixafor (SSNP). Decision tree models populated with data from a first-of-a-kind patient registry in six Czech centers (n = 93) were built to compare clinical benefits and direct costs from the payer's perspective. The success rates and costs for POD, SSP and SSNP mobilizations were; 94.9%, $7,197; 94.7%, $8,049; 84.7%, $5,991, respectively. The direct cost per successfully treated patient was $7,586, $8,501, and $7,077, respectively. The cost of re-mobilization of a poor mobilizer was $5,808 with G-CSF only and $16,755 if plerixafor was added. The total cost of plerixafor “on-demand” in the sub-cohort of poor mobilizers was $17,120. Generally, plerixafor improves the mobilization success by 10% and allows an additional patient to be successfully mobilized for incremental $11,803. Plerixafor is better and cheaper if used “on demand” than within a subsequent remobilization. J. Clin. Apheresis 28:395–403, 2013. © 2013 Wiley Periodicals, Inc.