We analyzed 338 adult patients with acute myeloid leukemia (AML) with t(8;21) and inv(16) undergoing stem cell transplantation (SCT) who were registered in the Japan Society for Hematopoietic Cell Transplantation database. At 3 years, overall survival (OS) of patients with t(8;21) and inv(16) was 50% and 72%, respectively (P = .002). Although no difference was observed when restricted to allogeneic SCT in first complete remission (CR; 84% and 74%), OS of patients with t(8;21) and inv(16) undergoing allogeneic SCT in second or third CR (45% and 86% at 3 years; P = .008) was different. OS was not different between patients in first CR who received allogeneic SCT and those who received autologous SCT for both t(8;21) AML (84% vs 77%; P = .49) and inv(16) AML (74% vs 59%; P = .86). Patients with inv(16) not in CR did better after allogeneic SCT than those with t(8;21) (70% and 18%; P = .03). Patients with t(8;21) and inv(16) should be managed differently as to the application of SCT. SCT in first CR is not necessarily recommended for inv(16). For t(8;21) patients in first CR, a prospective trial is needed to clarify the significance of autologous SCT and allogeneic SCT over chemotherapy.