We aimed to firstly explore characteristics and prognostic factors of therapy-related acute myeloid leukemia (t-AML) in multi-center samples in China. We analyzed 228 t-AML patients from 14 centers across China. The median age at t-AML diagnosis was 52 years (range, 1.3-89 years). The median latency interval was 45.8 months (19.2-142.8 months). Next generation sequencing (NGS) results were available in 150 (65.8%) patients. The overall survival (OS) and disease-free survival rates of all t-AML were 58.3% and 63.7%, respectively. In t-AML patients, NPM1 mutation (85.0% vs. 54.4%, P=0.01), core binding factor (CBF) (RUNX1/RUNX1T1 and CBF beta/MYH11) (70.7% vs. 55.1%, P=0.03), and allogeneic hematopoietic stem cell transplantation (allo-HSCT) (86.0% vs. 67.9%, P=0.02) were associated with significantly better OS, while the 2022 ELN intermediate-adverse risk group had worse OS than the favorable group (55.9% vs. 73.1%, P=0.02). In multivariable analyses, NPM1 mutation, CBF t-AML, primary tumor remission, WBC count <= 15x109 L-1, CRc after one course and allo-HSCT were associated with favorable OS. Regarding NGS molecular analysis, in addition to the positive effects of NPM1 on OS, our study identified TP53 mutation as a risk factor associated with poor OS (40.0% vs. 66.6%, P=0.03, HR=2.64). We developed a prognostic scoring system including clinical and molecular profiles termed NTCTH (NPM1 (HR=0.16), TP53 (HR=3.45), CBF t-AML (HR=0.09), first course intensive induction Therapy regime (HR=0.24), and allo-HSCT (HR=0.36)) in patients who performed NGS. Our study first demonstrated prognostic factors of t-AML in large samples from multiple centers in China and found that NPM1 and CBF t-AML were associated with superior OS, and TP53 was associated with inferior OS.