To evaluate the potential of allogeneic hematopoietic cell transplantation (HCT) with a reduced-intensity conditioning regimen (RIST) for the treatment of patients with hematologic malignancies not in remission, we retrospectively reviewed the medical records of 132 patients (89 leukemia or myelodysplastic syndrome, 40 malignant lymphoma, and 3 others) who received conventional myeloablative HCT (CST, n=52) or RIST (n=80). The median age of the RIST group was significantly higher than that of the CST group (53 years versus 40 years, P<.01). The RIST group also included a higher proportion of patients with an HCT-specific comorbidity index (HCT-CI) of 1 or more than the CST group (65% versus 37%, P=.03). The probabilities of achieving complete remission and the incidences of grades II-IV and III-IV acute graft-versus-host disease (aGVHD) in the CST and RIST groups were, respectively, 77% and 64%, 50% and 50%, and 23% and 28%, with no significant differences. Similarly, there was no difference in the 2-year probabilities of nonrelapse mortality (NRM, 36% and 38%), progressive disease or relapse (PD 51% and 49%), overall survival (OS, 31% and 38%), and progression-free survival (PFS, 28% and 29%). Multivariate analyses revealed that a higher HCT-CI score and transplant from donors other than HLA-matched relatives were associated with increased risks of NRM and poor OS, and patients who received chemotherapy within 2 months before HCT were associated with increased risks of PD, poor OS, and PFS after transplantation. After adjusting for these variables, the risks of NRM, PD, OS, and PFS in the RIST group were not significantly different from those in the CST group. In conclusion, these results suggest that the antileukemia/lymphoma effect associated with RIST is comparable to that associated with CST. RIST appears to be feasible for the treatment of hematologic malignancies not in remission.