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Autologous stem cell transplant (ASCT) is a feasible treatment option for multiple myeloma (MM) patients with renal insufficiency; however, these patients tend to experience higher rates of drug toxicity and transplant-related mortality (TRM) during ASCT. Recent adoption of bortezomib-based induction regimens and dose reduction of melphalan during conditioning may improve outcomes in this population. In this single center retrospective study, we compared the toxicity and survival outcomes of 96 MM patients with renal insufficiency undergoing ASCT between two eras: 1998-2007 and 2008-2016. The proportion of dialysis dependent patients was similar in both groups (49 and 45%). We found no TRM in those transplanted more recently as compared with 13% in the older era of ASCT. There were significantly more high grade (grades 3-4) toxicities in the older era of ASCT including high grade electrolyte abnormalities, mucositis, delirium, and bleeding. Patients transplanted more recently had significantly higher overall response rate (ORR) as well as deeper responses to ASCT (≥VGPR in 79% vs 39%). Progression-free survival (PFS) was prolonged by 26 months in the more recent era compared with the older era. Overall, improvements in treatment regimens have resulted in reduced TRM and toxicities for patients with renal insufficiency undergoing ASCT.