Background: PBSC mobilization (MOB) and apheresis is mandatory prior to ASCT and pose clinical, logistical, and financial challenges at transplant centers. This has resulted in considerable practice variation and a variety of local algorithms. Traditionally MOB was performed using G-CSF in the recovery phase after administration of chemotherapeutic agents such as cyclophosphamide (CTX). G-CSF alone (G) or G-CSF w/plerixafor (G+P) are other options. We compared the current US patterns of mobilization in a prospective observational study between OCT2017 and SEP2019. Methods: Consecutive pts (n = 690) undergoing MOB for upfront MM ASCT were prospectively enrolled from 20 participating centers. Specially designed data collection forms were used to collect resource utilization and complications in the peri-mobilization period. Based on a presurvey of center practices, 4 patterns of MOB were identified: CTX, G, G+P, or P Rescue of suboptimal G MOB. Results: CTX was the least common strategy (n = 52) followed by G (95) or G+P (252) or P Rescue (291). Presumed disease control and center preference were reasons for using CTX. Pt and disease characteristics were similar among groups with notable exceptions: CTX was less common in pts with higher SCr and more in those with higher beta2 microglobulin. CTX group had fewer pts in ≥VGPR status (31% vs. 60-71%). Triplet induction was used in 83% (RVD in 73% of pts) and resulted in ≥VGPR status in 61%. CTX was associated with 26% incidence of complications including a 4% hospitalization rate. Blood/platelet transfusions were needed in 15 and 12% respectively in CTX group but < 3% in other groups. A median of 8 million/kg CD34 cells were collected across all groups. Apheresis was completed in 2 days in 89% of G+P group vs. 70-75% of pts in the other groups. MOB was successful in 99% of cases overall with only 10 pts needing remobilization. 33% of CTX MOBand 63% of P Rescue group needed P resulting in 66% overall P use. With 98% pts still alive,clinical results of ASCT are not mature. Conclusions: CTX MOB is less used in clinical practice in the US for MM while P use was 66% in this large prospective study. CTX MOB seems to be preferred in some centers in those with suboptimal induction responses but was associated with higher complication rate. Planned G+P approach resulted in the fastest time to goal and less apheresis sessions. These data should inform overallMOB decision-making in the era of increasing apheresis needs for cellular therapies.