Background: Plerixafor enhances the ability of filgrastim (FIL) to mobilize CD34+ cells but adds cost to the mobilization. We hypothesized that replacing weight-based FIL with flat-dose pegfilgrastim (PEG) in a validated cost-based mobilization algorithm for patient-adapted use of plerixafor would add convenience without increased cost. Study design and methods: A single-center retrospective analysis compared two consecutive cohorts undergoing FIL or PEG mobilization before autologous hematopoietic stem cell transplantation for multiple myeloma or lymphoma. FIL dose was 10 Âμg/kg/day continuing until completion of collection and a 12-mg flat dose of PEG. Peripheral blood CD34+ cells (PB-CD34+) enumeration was performed on the fourth day after initiation of growth factor. Subjects surpassing a certain target-specific threshold of PB-CD34+ started apheresis immediately while subjects with lower PB-CD34+ received plerixafor with apheresis starting on the fifth day. Results: Overall 68 of 74 in the FIL group and 52 of 57 patients in the PEG group met the mobilization target. Only one patient in each cohort required remobilization. Median PB-CD34+ on Day 4 was significantly higher in patients in the PEG group (18.1 × 106 vs. 28.7 × 106 cells/L, p = 0.01). Consequently, patients in the PEG group were less likely to require administration of plerixafor (67.5% vs. 45.6%, p = 0.01). Cohorts had near identical mean number of apheresis sessions and comparable CD34+ yield. The estimated cost associated with growth factor was higher in patients in the PEG group, but it was counterbalanced by lower cost associated with use of plerixafor. Conclusion: Single administration of 12 mg of PEG is associated with better CD34+ mobilization than FIL allowing for effective, convenient mobilization with less frequent use of plerixafor. © 2012 American Association of Blood Banks.