Relapse is the overwhelming cause of treatment failure after autologous transplantation for multiple myeloma (MM). For patients with a syngeneic donor, twin transplants provide a healthy graft that is free of myeloma. The relative impact of the graft on posttransplant relapse can be estimated by comparing risk of relapse after hematopoietic cell transplantation from genetically identical twins versus autotransplants because confounding differences in minor or major histocompatibility antigens are absent in the syngeneic transplant setting. Outcomes of 43 subjects who received twin transplants for MM were compared to 170 matched autotransplant recipients reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). Multivariate analysis was performed by fitting a Cox model stratified on matched pairs. The matched transplant patients studied were similar with respect to subject-, disease-, and transplant-related characteristics. Cumulative incidence of relapse/progression was significantly lower, and progression-free survival (PFS) was significantly higher following twin transplants. In multivariate analysis, the probability of relapse/progression was lower in twins (relative risk [RR] = 0.49, 95% confidence interval [CI] 0.28-0.86, P = .011). Twin transplants have a significantly lower relapse risk than autotransplants in MM, suggesting that graft composition may impact outcomes following high-dose chemotherapy.