Background: Autologous stem cell transplant (ASCT) remains part of standard therapy for Multiple Myeloma (MM). Lenalidomide (LEN) is a newer, effective therapy for MM. It has been suggested that prior LEN therapy is associated with an increased risk of stem cell collection failure, particularly when only G-CSF is used for mobilization. Methods: We conducted a retrospective chart review of 310 consecutive MM pts who underwent pheresis to collect stem cells for first ASCT between July 1, 2007 and June 30, 2011 at the Karmanos Cancer Institute. We compared differences in quantity of CD34 cells collected, days needed to collect the target number of cells (> 2.5 x 10*6 CD34+ cells/kg), days to platelet and neutrophil engraftment. We also evaluated the association between CD34+ cells collected and the number of cycles of LEN therapy. Results: Of 310 patients, 90% were mobilized with only G-CSF initially. Patients were analyzed as two groups: LEN exposed (LEN(+); n = 128) and LEN naive(LEN(-); n = 182). Median age in both groups was 58 years. No differences in race, sex and MM stage distribution were observed between the two groups. The median number of stem cells collected in the LEN(+) group was significantly less than the LEN(-) group (6.46 vs. 7.56 x 10*6 CD34 cells/kg; p= 0.0004). In addition, the median number of pheresis sessions required for adequate stem cell collection were significantly more in the LEN(+)group as compared to LEN(-) group (2 vs.1 sessions; p=0.002). In the LEN(+) group, there was a negative correlation between CD34+ cells collected and the prior number of cycles of LEN (p=0.0001). There was no statistically significant excess in the number of stem cell collection failures with G-CSF in the LEN(+) group (7% vs. 4% p=0.31). All pts who failed collection after G-CSF were successfully collected with Cytoxan or Plerixafor priming. LEN exposure had no effect on post-ASCT neutrophil or platelet recovery. Conclusions: Although Lenalidomide exposure is associated with a slightly lower CD34+ stem cell yield and on average an extra session of pheresis when G-CSF is used for mobilization, collection failure is uncommon and post-ASCT engraftment is normal.