Acute promyelocytic leukemia (APL) is the most curable subtype of acute myeloid leukemia. Second complete remission (CR2) can be easily achieved with several therapeutic options even after relapse. However, the optimal strategy to treat APL in CR2 is still controversial. We retrospectively compared the outcome of autologous (auto) and allogeneic (allo) hematopoietic stem cell transplantation (HSCT) for patients with APL in CR2 or CR3. Fifteen patients received auto and 13 received allo HSCT between 1999 and 2004 at eight hospitals belonging to the Nagoya Blood and Marrow Transplantation Group. Four-year disease-free survival (DFS) and overall survival (OS) for autografted patients were 68.9 and 75.8%, whereas those for allografted patients were 46.2 (P = 0.350) and 46.2% (P = 0.185), respectively. Three autografted patients and one allografted patient relapsed, and one autografted patient and five allografted patients died without leukemia relapse. Among 14 autografted patients who were evaluated for MRD with molecular analysis, relapse occurred in one with positive MRD (n = 2) and two with negative MRD (n = 12). These data suggest that auto HSCT is very effective for APL in CR2 or CR3, and may be preferable to allo HSCT for a portion of patients. Prospective studies are required to define the role of auto HSCT in the treatment of relapsed APL.