Recent studies have reported that high mean corpuscular volume (MCV) might be associated with mortality in patients with advanced chronic kidney disease (CKD). However, the question of whether a high MCV confers a risk for mortality in Japanese patients remains unclear. We conducted a longitudinal analysis of a cohort of 8571 patients using data derived from the Japan Dialysis Outcomes and Practice Patterns Study (J-DOPPS) phases 1 to 5. Associations of all-cause mortality, vascular events, and hospitalization due to infection with baseline MCV were examined via Cox proportional hazard models. Non-linear relationships between MCV and these outcomes were examined using restricted cubic spline analyses. Associations between time-varying MCV and these outcomes were also examined as sensitivity analyses. Cox proportional hazard models showed a significant association of low MCV (< 90 fL), but not for high MCV (102 < fL), with a higher incidence of all-cause mortality and hospitalization due to infection compared with 94 ≤ MCV < 98 fL (reference). Cubic spline analysis indicated a graphically U-shaped association between baseline MCV and all-cause mortality (p for non-linearity p < 0.001). In conclusion, a low rather than high MCV might be associated with increased risk for all-cause mortality and hospitalization due to infection among Japanese patients on hemodialysis.