The impact of novel drugs for treating multiple myeloma (MM) on the utilization and outcomes of autologous hematopoietic progenitor cell transplantation (AHPCT) is unknown. We reviewed characteristics and outcomes of 20,278 patients who underwent AHPCT within 12months of diagnosis of MM in the United States and Canada and registered at the Center for International Blood and Marrow Transplant Research (CIBMTR) in 3 time cohorts reflecting the increasing availability of novel drugs: 1995 to 1999 (n=2226), 2000 to 2004 (n=6408), and 2005 to 2010 (n=11,644). In the United States, the number of AHPCTs performed increased at a greater rate than new MM cases. Patients in recent cohorts were older, less likely to have stage 3MM, and more likely to have received previous thalidomide, lenalidomide, or bortezomib. On multivariate analysis, AHPCT in the 2000 to 2004 cohort (HR=0.77) or in the 2005 to 2010 cohort (HR=0.68) were associated with lower risk of death. Survival at 60months post-AHPCT improved from 47% in 1995 to 1999 to 55% in 2000 to 2004 and to 57% in 2005 to 2010, owing less to improvement in progression-free survival (50% versus 55% versus 57% at 24months) than to postrelapse/progression survival (58% versus 65% versus 72% at 24months). AHPCT and new biological agents are complementary, nonredundant therapies and should be combined in the management of MM in suitable patients. © 2013 American Society for Blood and Marrow Transplantation.