We compared the outcomes of unrelated donor (URD, n = 358) with human leukocyte antigen (HLA) - matched sibling donor (MSD, n = 226) transplantations in patients with acute myeloid leukemia (AML) in first complete remission (CR1) having unfavorable cytogenetics at diagnosis. Unfavorable cytogenetic abnormalities were: complex (≥ 3 abnormalities), 32%; and noncomplex involving chromosome 7, 25%; chromosome 5, 9%; 11q or MLL rearrangements, 18%; t(6;9), 5%; and other noncomplex, 10%. URDs were HLA-well-matched (n = 254; 71%) or partially-matched (n = 104; 29%). Three-year leukemia-free survival (LFS) for MSD was 42% (95% confidence interval [CI], 35%-48%) compared with 34% (95% CI, 28%-41%) for HLA-well-matched URD and 29%(95% CI, 20%-39%) for partially-matched URD (P = .08). In multivariate analysis, HLA-well-matched URD and MSD yielded similar LFS (relative risk [RR] = 1.1, 95% CI, 0.86-1.40, P = .44) and overall survival (OS; RR = 1.06, 95% CI, 0.83-1.37, P = .63). LFS and OS were significantly inferior for HLA-partially-matched URD recipients, those with prior myelodysplastic syndrome, and those older than 50 years. All cytogenetic cohorts had similar outcomes. Patients with chronic graft-versus-host disease had a significantly lower risk of relapse (RR = 0.68, 95% CI, 0.47-0.99, P = .05). Hematopoietic cell transplantation (HCT) using HLA-well-matched URD and MSD resulted in similar LFS and OS in AML patients in CR1 with unfavorable cytogenetics. Outcomes of HCT from HLA-partially-matched URD were inferior.