The outcomes for allogeneic hematopoietic cell transplantation (allo-HCT) are heavily influenced by non-relapse mortality (NRM). We retrospectively assessed the changes in the incidence and causes of NRM after allo-HCT over the past 12 years. NRM, relapse rate and OS were analyzed using the Japan transplant outcome database of 6501 adult patients with acute leukemia or myelodysplastic syndrome who received their first allo-HCT in remission from 1997 through 2008. In multivariate analysis in patients aged 16-49 years, the adjusted hazard ratios (HRs) for NRM for 2001-2004 and 2005-2008 were 0.78 (95% confidence interval, 0.65-0.93) and 0.64 (0.54-0.78), respectively, compared with 1997-2000. The HR for overall mortality in 2005-2008 was 0.81 (0.70-0.93) compared with 1997-2000. In patients aged 50-70 years, the HRs for NRM and overall mortality in 2005-2008 were 0.56 (0.46-0.68) and 0.66 (0.47-0.93), respectively, compared with those in 2001-2004. We found that causes of death that contributed to the changes in NRM varied among subgroups. In conclusion, our study indicated that the incidence of NRM after allo-HCT has significantly decreased over the past 12 years, which has led to an improvement of OS, and also showed reductions in NRM in subgroups consisting of older patients and those who received unrelated cord blood transplantation.