Few clinical protocols have focused on patients with therapy-related myeloid neoplasms (t-MN). Therefore, we enrolled 32 patients with previously untreated t-MN on a clinical trial testing the effectiveness of a unified induction regimen of high-dose cytarabine and mitoxantrone. The complete remission (CR) rate was 66% (95% CI 47-81%) and the partial remission (PR) rate was 16% (95% CI 5-33%), for an overall response rate of 82%. Day 30 treatment mortality was 9% (3/32), and the most serious induction toxicity was cardiac dysfunction. Among the patients with CR, 13 (62%) received consolidation therapy using an allogeneic hematopoietic cell transplant (HCT), four (21%) received an autologous HCT, and three (16%) received further chemotherapy. We observed long-term disease-free survival in patients who received all three types of consolidation therapy. The remission induction of high-dose cytarabine and mitoxantrone for t-MN is a well-tolerated efficacious combination, which allows aggressive consolidation and long-term disease-free survival.