Monosomal karyotype (MK), defined as ≥ 2 autosomal monosomies or a single monosomy in the presence of other structural abnormalities, was confirmed by several studies to convey an extremely poor prognosis in patients with acute myeloid leukemia (AML) with a 4-year overall survival after diagnosis of < 4%. A recent investigation by the Southwest Oncology Group found that the only MK(+) patients alive and disease free > 6 years from diagnosis received allogeneic hematopoietic cell transplantation (HCT). To expand this observation, we retrospectively analyzed 432 patients treated with HCT at the Fred Hutchinson Cancer Research Center, 14% of whom were MK(+). The 4-year overall survival of patients after HCT was 25% for MK(+) AML and 56% for MK(-) AML (adjusted hazard ratio = 2.29, P < .0001). Among the MK(+) patients, complex karyotype was associated with a significantly worse outcome than patients with noncomplex karyotype (adjusted hazard ratio = 2.70, P = .03). Thus, although the prognosis of MK(+) patients remains worse than that for MK(-) patients in the transplantation setting, HCT appears to improve the overall outcome of MK(+) patients, especially patients without a complex karyotype. However, the 28% of MK(+) patients > 60 years had only a 6% 4-year survival rate after HCT, stressing the need for new approaches in these patients.