We sought to determine whether patients with hematologic malignancies treated by nonmyeloablative hematopoietic cell transplantation (HCT) at a single institution between December 1997 and June 2006 had worse outcomes with grafts from unrelated donors (URDs) (n = 184) compared with HLA-identical related donors (n = 221). The nonmyeloablative preparative regimen consisted of 2 Gy of total body irradiation (TBI) with (78%) or without (22%) fludarabine, along with posttransplantation mycophenolate mofetil (MMF) and cyclosporine (CSa). After adjusting for the HCT comorbidity index, relapse risk, patient age, stem cell source, preparative regimen, previous cytomegalovirus (CMV) infection, and sex mismatch of donor and recipient in multivariate analysis, we found no statistically significant differences between unrelated and related HCT recipients in terms of risk of nonrelapse mortality (NRM; hazard ratio [HR] = 0.98; 95% confidence interval = 0.6-1.6; P = .94), relapse (HR = 1.04; 95% confidence interval = 0.7-1.5; P = .82), or overall mortality (HR = 0.99; 95% confidence interval = 0.7-1.4; P = .94). Overall rates of severe acute and extensive chronic graft-versus-host disease (aGVHD, cGVHD) also were not significantly different between the 2 groups. We conclude that within the limitations of a retrospective study, these results indicate that candidates for nonmyeloablative HCT without suitable related donors may expect similar outcomes with grafts from URDs.