Therapy-related acute myeloid leukemia (t-AML), a life-threatening complication of cytotoxic therapy, represents an emerging challenge of modern oncology.Evaluation of t-AML clinical outcomes, considering genetic changes and treatment intensity.We conducted a retrospective analysis of all consecutive AML patients from one hematology center (hospitalisation between 2000-2021). t-AML diagnosis was established according to the 2016 WHO criteria. Overall survival (OS) and progression free survival (PFS) were defined to evaluate treatment outcomes. Retrospective identification of 17p13 deletion and TP53 mutation was conducted.Among 743 AML patients, 60 (8.1%) were diagnosed with t-AML (63.4% with previous solid tumors). Complex karyotype (CK) and 17p13 deletion were detected in 26.8% and 26.7% of t-AML, respectively, while FLT3-ITD and TP53 mutations occurred in 15.4% and 12.5% t-AML. Median OS and PFS were 13 and 8 months, respectively. Survival outcomes were superior for alloHCT treatment than intensive chemotherapy alone (median OS: 47 vs 7 months, P=0.01). APL patients did not reach median OS and worse survival was noted within CK than non-CK t-AML (median OS: 6 vs 24 months, P=0.02). In intensively treated t-AML, survival was better for patients under 64 years of age (P=0.03). In the multivariable Cox proportional hazards regression model, alloHCT was associated with superior OS (HR=0.19, 95% CI=0.04-0.91, P=0.04). Moreover, we noted high frequency of treatment-related complications of t-AML.Our study revealed that prognosis of t-AML varies. Hence, the treatment strategy should rely on performing alloHCT as soon as possible in patients with adverse genetics.