Collection of hematopoietic progenitor cells (HPC) after previous autologous hematopoietic progenitor cell transplant (aHCT) was studied in 221 patients with multiple myeloma (MM). With a total of 333 collections, the median number of CD34+ cells collected was 4.7 × 10(6) CD34+ cells/kg, and 74% of the patients collected ≥ 2.5 × 10(6) CD34+ cells/kg. Among 26 variables examined, the strongest predictor for poor collection was a platelet count <100 × 10(6)/l before mobilization (P<0.001). A subsequent aHCT was performed in 154 of the 221 patients. Sole use of HPC procured after aHCT in 86 patients was associated with delayed platelet recovery (P<0.001) and linked to development of myelodysplastic syndrome (MDS)-associated cytogenetic abnormalities (MDS-CA; P=0.027, odds ratio (OR) 10.34) and a tendency towards clinical MDS/acute myeloid leukemia (AML; P=0.091, OR 3.57). However, treatment-related mortality (P=0.766) and time to absolute neutrophil count recovery ≥0.5 × 10(9)/l (P=0.879) were similar to when a pre-aHCT graft was used. Indeed, adding HPC collected before any aHCT neutralized the risk of MDS-CA or MDS/AML. Therefore, we advise generous initial HPC collection to broaden the salvage armamentarium for patients with MM.