Autologous stem cell transplantation remains a clinical option to consolidate some adult patients with acute myelogenous leukemia (AML) in first complete remission (CR1). In a small cohort of patients, we have previously shown better outcomes following Busulfan and Melphalan (BUMEL) over Busulfan and Cyclophosphamide (BUCY). To identify the subpopulations that might get the highest benefit with BUMEL, we designed a larger study. All adult patients with primary AML and available cytogenetics, autografted from January 2000 to December 2016 in CR1, were included: 1137 patients received BUCY and 512 BUMEL. All factors differing in distribution between the 2 conditioning groups were introduced in multivariate analyzes. In a primary analysis, we found an interaction between conditioning and the poor risk group defined as poor cytogenetics and/or presence of the FLT3-ITD mutation. During analysis of the poor risk group, 176 patients received BUCY and 62 BUMEL. BUMEL was associated with a lower RI at 5 years (53% versus 69%, HR: 0.52, P =.002), a better Leukaemia-free survival (LFS) (42% versus 25%, HR: 0.54, P =.002) and a better OS (54% versus 36%, HR: 0.61, P =.02). During analysis of the non poor risk group, 961 patients received BUCY and 450 BUMEL. At 5 years, the RI was 50% and 47%, the LFS 45% and 48% and the OS 56% and 60% respectively, with no significant difference. We conclude that BUMEL is the preferable conditioning regimen for the poor risk leukemic patients, while in AML patients without poor risk cytogenetics or FLT3 both conditioning regimens are valid.