ABSTRACT: Red cell distribution width (RDW) is an index of red blood cell volume variability that has historically been used as a marker of iron deficiency anemia. More recently, studies have shown that elevated RDW is associated with higher mortality risk in the general population. However, there is lack of data demonstrating the association between RDW and mortality risk in hemodialysis (HD) patients. We hypothesized that higher RDW is associated with higher mortality in HD patients.Retrospective observational study using a large HD patient cohort.109,675 adult maintenance HD patients treated in a large dialysis organization from January 1, 2007, to December 31, 2011.Baseline and time-varying RDW, grouped into 5 categories: <14.5%, 14.5% to <15.5%, 15.5% to <16.5%, 16.5% to <17.5%, and ?17.5%. RDW of 15.5% to <16.5% was used as the reference category.All-cause mortality.Mean age of study participants was 63±15 (SD) years and the study cohort was 44% women. In baseline and time-varying analyses, there was a graded association between higher RDW and incrementally higher mortality risk. Receiver operating characteristic, net reclassification analysis, and integrated discrimination improvement analyses demonstrated that RDW is a stronger predictor of mortality as compared with traditional markers of anemia, such as hemoglobin, ferritin, and iron saturation values.Lack of comprehensive data that may be associated with both RDW and HD patient outcomes, such as blood transfusion data, socioeconomic status, and other unknown confounders; therefore, the possibility of residual confounding could not be excluded. Also, lack of information for cause of death; thus, cardiovascular mortality outcomes could not be examined.In HD patients, higher RDW is associated with incrementally higher mortality risk. RDW is also a stronger predictor of mortality than traditional laboratory markers of anemia. Further studies are needed to determine the mechanisms underlying the association between RDW and mortality.