FLT3-ITD and NPM1 mutation refine prognostic stratification in acute myeloid leukemia (AML) with intermediate-risk cytogenetics. However, data on their role in patients undergoing autologous stem cell transplantation (Auto-SCT) as postremission therapy (PRT) are limited. We therefore sought to retrospectively evaluate the role of FLT3-ITD and NPM1 in a cohort of AML patients (n = 405) with intermediate-risk cytogenetics, autografted in first complete remission (CR1). Patients were transplanted between 2000 and 2014 and reported to the European Society for Blood and Marrow Transplantation (EBMT) registry. Leukemia-free survival (LFS) was the primary outcome. Median follow-up was 5.5 years. FLT3-ITDneg/NPM1WT was the leading molecular subtype (50%), followed by FLT3-ITDneg/NPM1mut (30%). In the univariate analysis, molecular subtype was associated with LFS, overall survival (OS), and relapse incidence (RI) (p < 0.001); 5-year LFS: FLT3-ITDneg/NPM1mut 62%, FLT3-ITDpos/NPM1mut 38%, FLT3-ITDneg/NPM1WT 32%, and FLT3- ITDpos/NPM1WT 21%. At 5 years, OS and RI in the FLT3-ITDneg/NPM1mut subtype were 74% and 35%, respectively. The corresponding OS and RI in other subtypes were below 48% and over 57%. In a Cox multivariable model, molecular subtype was the strongest predictor of LFS, OS, and relapse. In conclusion, AML patients with intermediate-risk cytogenetics and FLT3-ITDneg/NPM1mut experience favorable outcomes when autografted in CR1, suggesting that AutoSCT is a valid PRT option.