The prognosis of therapy-related myelodysplastic syndrome and acute leukemia (t-MDS/AL) remains poor. We retrospectively analyzed the data of 47 patients (31 AL and 16 MDS) who were treated at our institute. Thirty-three patients received disease-adapted chemotherapy, with a response rate of 73%, while 14 received no interventions due to an indolent course, such as MDS. The median follow-up of surviving patients was 1.9 years (range 0.1-10.5) after the diagnosis of t-MDS/AL, and the estimated 3-year overall survival (OS) for all patients was 55%. Twenty-seven patients underwent allogeneic hematopoietic stem cell transplantation (HCT), and the 3-year non-relapse mortality was 17%. Twenty patients did not undergo HCT due to various reasons including advanced age or comorbidities. The 3-year OS was better in patients who received HCT than in those who did not (71 vs. 31%; p = 0.018). A multivariate analysis revealed that HCT was associated with a better OS. Although this study has several limitations, including a potential selection bias due to the retrospective nature of the analysis and a small number of patients, the results show that modern HCT may be useful for inducing long-term survival in a fraction of patients suffering from t-MDS/AL. The present findings warrant future prospective studies.