BACKGROUND: It is widely accepted that allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only potentially curative option available for secondary Acute Myeloid Leukemia (sAML). However, clinical factors impacting outcomes after allo-HSCT and the potential role of autologous-HSCT (auto-HSCT) in real-life series are needed. Previously, the PETHEMA group reported a series of 2310 patients with sAML within the nationwide registry. Out of them, 876 were candidates to receive chemotherapy and 274 patients (55 auto-HSCT and 219 allo-HSCT). OBJECTIVE: In this work, we have analyzed the role auto-HSCT (N=55) or allo-HSCT (N=219) as front-line treatment for sAML patients included in AML Spanish PETHEMA registry. In this paper, we analyze outcomes as well as prognostic variables in this series of patients undergoing auto- or allo-HSCT as part of the front-line treatment for sAML. STUDY DESIGN: We used the multinational PETHEMA AML registry (NCT02607059) to identify adult patients (age ≥18 years) with a diagnosis of sAML who received auto- or allo-HSCT as front-line treatment in Spanish and Portuguese institutions from August, 1 RESULTS: With a median follow-up of 32.7 months, better 5-year OS and LFS were obtained with allo-HSCT in CR1 (44.5% and 39.9%, respectively), as compared with auto-HSCT in CR1 (30% and 20.5%, respectively) but without reaching statistical differences for OS (p= 0.22 and p=0.03). The higher incidence of relapse in auto-HSCT is counterbalanced with the significantly low NRM rate. For allo-HSCT patients, 5-year outcomes were significantly influenced by the cytogenetic/genetic risk. In multivariate analysis, adverse cytogenetic/genetic risk group retained statistical significance for all endpoints. CONCLUSION: As conclusions, we confirmed the role of allo-HSCT as a potential curative option for patients and we report that auto-HSCT in CR can still provide a 5-year LFS of 20% in sAML patients. Finally, our results confirm adverse cytogenetic/genetic risk category as an independent negative factor in sAML patients receiving HSCT.