This retrospective report compared the results of graft source on outcome after allogeneic stem cell transplantation (allo-SCT) in patients with hematologic malignancies receiving a reduced intensity conditioning (RIC) regimen. A total of 152 patients received either a RIC allo-SCT using a 9/10 mismatched unrelated donor (MisMUD, n=42) or a double unrelated umbilical cord blood (dUCB, n=110) graft. With a median follow-up of 30.3 months, the cumulative incidence of non-relapse mortality was 26% in the dUCB group versus 24% in the MisMUD group (P=0.95). Grade 3-4 acute graft-versus-host disease (GVHD) incidence was 19.7% in the dUCB group versus 21.4% in the MisMUD group (P=0.83). The cumulative incidence of extensive chronic GVHD at 2 years was 6.4% in the dUCB group versus 21.4% in the MisMUD group (P=0.02). The Kaplan-Meier estimate of overall survival at 2 years was comparable between both groups (52.3% (95% confidence interval (CI), 42.1-61.5%) in the dUCB group versus 47.9% (95% CI, 31.6-62.4%) in the MisMUD group, P=0.55). Progression-free survival at 2 years was 43.3% (95% CI, 33.7-52.5%) in the dUCB group versus 38.3% (95% CI, 23.2-53.3%) in the MisMUD group (P=0.55). These data suggest that dUCB is a valid alternative graft source with significantly less chronic GVHD compared with MisMUD in the setting of RIC allo-SCT.