The goal of this analysis was to define the role of the moderate-intensity fludarabin Ara-C amsacrin (FLAMSA)-reduced intensity conditioning (RIC) regimen for patients with high-risk AML undergoing allogeneic SCT (alloSCT) in first CR1. High-risk was defined by (1) AML secondary to MDS or radio/chemotherapy, (2) unfavorable cytogenetics or (3) delayed response to induction chemotherapy. A total of 23 of 44 AML patients referred to the University of Munich for alloSCT in CR1 between 1999 and 2006 fulfilled these criteria and received FLAMSA chemotherapy, followed by RIC (4 Gy TBI/cyclophosphamide/ATG) for alloSCT. Twenty-two patients engrafted, one died in aplasia. Two-year cumulative incidences for relapse and nonrelapse mortality (NRM) were 4.6 and 22.5%, respectively. Four-year overall and leukemia-free survival was 72.7% (median follow-up among survivors: 35 months). The results of this high-risk cohort were compared to the outcome of 21 consecutive standard-risk patients <55 years, who had received standard, myeloablative sibling SCT in CR1 AML within the same center and time period. Survival and cumulative incidences of relapse and NRM were identical in both groups. In conclusion, the FLAMSA-RIC regimen produces long-term remission in a high proportion of patients with high-risk AML transplanted in CR1. In this cohort, FLAMSA-RIC showed equivalent antileukemic activity as compared to the standard protocols.