Molecular assessment of measurable residual disease (MRD) in NPM1-mutated AML patients is a powerful prognostic tool to identify the risk of relapse. There is limited data regarding MRD-guided decisions against alloSCT in elderly patients and FLT3-ITD co-mutation. We describe the outcome of NPM1-mutated AML patients in whom alloSCT was deferred based on ELN 2017 risk and MRD response. We report a relapse rate of 53% in this group, with a much higher incidence for older than 60 years patients than for younger patients (73% vs. 37%). When comparing outcomes of alloSCT in CR1 to intensive chemotherapy consolidation within each age group, patients over 60 years and patients with FLT3-ITD co-mutation had significantly lower RFS with intensive consolidation. Yet, in all subgroups, the lower RFS did not translate into OS difference, suggesting that relapsed NPM1 patients can often be salvaged and consequently achieve long-term remission. Our study supports the use of MRD response along with FLT3-ITD status in the decision to use post-remission therapy. We demonstrate that older patients and patients with FLT3-ITD-mutated AML have a high relapse rate but can be salvaged, leading to long-term survival.