A recent phase 3 trial showed that outcome of older patients with secondary acute myeloid leukemia (
AML
) may be improved by a liposomal encapsulation of cytarabine and daunorubicin (
CPX
‐351). This phase 3 study represents a unique example of prospective data in this rare subgroup providing basis for comparison with real life data. Here, we retrospectively assessed characteristics and outcome of patients aged 60‐75 years with secondary or therapy‐related
AML
in real life. Out of 218 patients that fulfilled
CPX
‐351 study criteria, 181 patients (83.0%) received antileukemic treatment either intensive chemotherapy (n = 121) or hypomethylating agents (
HMA
, n = 60). As compared with patients treated by chemotherapy,
HMA
‐treated patients were older, had lower
WBC
, more often
AML
with antecedent myelodysplastic syndrome and adverse cytogenetic risk. In chemotherapy‐treated patients, the complete response rate was 69%, median overall survival (
OS
) was 11 months whereas 3‐year and 5‐year
OS
was 21% and 17%, respectively. In
HMA
‐treated patients, the complete response rate was 15%, median
OS
was 11 months whereas 3‐year and 5‐year
OS
was 15% and 2%, respectively. In conclusion, although outcome of older patients with high‐risk
AML
is very poor, a significant proportion of patients treated by standard intensive chemotherapy but not
HMA
are long‐term survivors.