The clinical value of allogeneic and autologous hematopoietic stem cell transplantation (alloHSCT, autoHSCT) in the subtype of acute myeloid leukemia (AML) with double mutant CEBPA (CEBPAdm) has remained unsettled. Among 2983 patients analyzed for CEBPA mutational status (age 18-60 years) treated on four HOVON/SAKK and three AMLSG protocols; 124 had AML with CEBPAdm and achieved first complete remission (CR1). Evaluation of the clinical impact of alloHSCT and autoHSCT versus chemotherapy was performed by addressing time dependency in the statistical analyses. Thirty-two patients proceeded to alloHSCT from a matched related (MRD, n=29) or matched unrelated donor (MUD, n=3) and 20 to autoHSCT in CR1; 72 received chemotherapy. Relapse-free survival (RFS) was significantly superior in patients receiving an alloHSCT or autoHSCT in CR1 as compared to chemotherapy (p<0.001), whereas overall survival (OS) was not different (p=0.12). Forty-five patients relapsed. Of 42 patients treated with reinduction therapy, 35 achieved a second CR (83%) and most (n=33) patients received an alloHSCT (MRD, n=11; MUD, n=19; haplo-identical donor, n=3). Survival of relapsed patients measured from date of relapse was 46% after 3 years. Adult AML patients with CEBPAdm benefit from alloHSCT and autoHSCT; relapsed patients still have a favorable outcome after reinduction followed by alloHSCT. All patients had been included in 6 multicenter treatment trials, of which 5 had been published previously and one is registered at clinicaltrials.gov (NCT00151255).