Transfusion-associated iron overload could be an important risk factor in myeloablative hematopoietic stem cell transplantation. However, few studies have evaluated the effect of iron overload in reduced-intensity stem cell transplantation (RIST). We evaluated 38 patients with myeloid malignancies, 16 with and 22 without iron overload, who received RIST. We used pretransplant serum ferritin as a marker of iron overload. There was a positive correlation between the number of transfused packed red blood cells and pretransplant serum ferritin levels (21.5 units and 1,578.7 microg/l in the iron overload group vs. 12 units and 739.3 microg/l in the iron non-overload group; p <0.01). Engraftment day and chimerism analysis were not affected by iron overload (p = 0.71 and 0.47, respectively). There were no differences in treatment-related mortality (p = 0.94), veno-occlusive disease (p = 0.99), acute and chronic graft versus host disease (p = 0.58 and 0.99, respectively) according to iron overload. There was a significant difference in disease-free and overall survival (35.8 and 27% in the iron overload group vs. 80.6 and 54.6% in the iron non-overload group; p = 0.01 and 0.03, respectively). We conclude that transfusion-associated iron overload is an adverse risk factor in RIST for myeloid malignancies. The clinical outcomes according to iron overload in RIST were different in myeloablative hematopoietic stem cell transplantation. A serial follow-up of serum ferritin level and judicious iron chelation therapy will be needed to manage the side effect of iron overload in RIST and improve transplantation outcomes.