Background: Eosinophils are traditionally known as moderators of allergic reactions; however, they have now emerged as one of the principal immune-regulating cells as well as predictors of vascular disease and mortality in the general population. Although eosinophilia has been demonstrated in hemodialysis (HD) patients, associations of eosinophil count (EOC) and its changes with mortality in HD patients are still unknown. Methods: In 107 506 incident HD patients treated by a large dialysis organization during 2007-11, we examined the relationships of baseline and time-varying EOC and its changes (?EOC) over the first 3 months with all-cause mortality using Cox proportional hazards models with three levels of hierarchical adjustment. Results: Baseline median EOC was 231 (interquartile range 155-339) cells/?L and eosinophilia (>350 cells/?L) was observed in 23.4% of patients. There was a gradual increase in EOC over time after HD initiation with a median ?EOC of 5.1 (IQR -53-199) cells/?L, which did not parallel the changes in white blood cell count. In fully adjusted models, mortality risk was highest in subjects with lower baseline and time-varying EOC (<100 cells/?L) and was also slightly higher in patients with higher levels (?550 cells/?L), resulting in a reverse J-shaped relationship. The relationship of ?EOC with all-cause mortality risk was also a reverse J-shape where both an increase and decrease exhibited a higher mortality risk. Conclusions: Both lower and higher EOCs and changes in EOC over the first 3 months after HD initiation were associated with higher all-cause mortality in incident HD patients.