Hematopoietic cell transplantation (HCT) is an effective treatment for myelodysplasia (MDS) and secondary acute myeloid leukemia (sAML). In this study, outcome of 593 patients with MDS/sAML after autologous and allogeneic HCT from a matched unrelated donor (MUD) were compared. A total of 167 (28%) patients received HCT from MUD without prior chemotherapy (MUD-U). The rest received HCT in first complete remission (CR1) (Autologous (Auto-CR1), n=290 (49%), HCT from MUD (MUD-CR1), n=136 (23%)). Survival at 3 years was best in MUD-CR1 (50%) compared to Auto-CR1 (41%) and MUD-U (40%) (P=0.01). Similarly, disease-free survival was 44% for MUD-CR1 compared to Auto-CR1 (28%) and MUD-U (34%) (P=0.03). Treatment-related mortality was 17% in Auto-CR1 compared to MUD-CR1 (38%) and MUD-U (49%) (P<0.001). Relapse for Auto-CR1 was 62% compared to 24 and 30% for MUD-CR1 and MUD-U, respectively (P<0.001). Outcome was best for patients with low tumor burden transplanted 6-12 months after diagnosis. Factors influencing outcome at 3 years were mainly significant in the first 6 months. Only, relapse after autologous HCT remained constant over time. Outcomes after allogeneic HCT in patients of 20-40 and >40 years were similar. Autologous and Allogeneic HCT from MUD offer the possibility of long-term survival to patients with MDS/sAML.