Iron overload is common in patients undergoing allogeneic hematopoietic cell transplantation (HCT) for hematologic disorders. Serum ferritin, a marker of tissue iron overload, was measured immediately before transplant in adult patients undergoing myeloablative HCT from matched sibling or unrelated donors. The effect of elevated pretransplant ferritin (defined as ferritin >or=1000 ng/ml) on day 100 mortality, overall survival, acute GVHD and infectious complications was assessed. Data on 190 patients were analyzed. In univariate analysis, the high-ferritin group had increased day 100 mortality (20 vs 9%, P=0.038), decreased overall survival (log-rank test: P-value=0.004), increased acute GVHD/death (63 vs 43%, P=0.009) and increased incidence of blood stream infections (BSIs)/death (60 vs 44%, P=0.042). In a multivariate analysis, high ferritin was associated with increased risk of death (Cox model: hazard ratio=2.28, P=0.004), increased day 100 mortality (generalized linear model (GLM) odds ratio=3.82, P=0.013), increased incidence of acute GVHD/death (GLM odds ratio=3.11, P=0.001) and increased risk of BSI/death (GLM odds ratio=1.99, P=0.032). The results remained similar when serum ferritin was considered a continuous variable. Elevated serum ferritin adversely impacts on overall survival and increases the likelihood of acute GVHD and BSI after allogeneic HCT.