Western guidelines recommend the use of intravenous iron supplementation for hemodialysis patients. However, in Japanese patients with well-controlled inflammation, iron replacement may be achieved with oral iron supplementation. This study involved 108 courses in 77 outpatient hemodialysis patients who received low-dose oral iron replacement therapy. Data from baseline to week 28 of treatment were analyzed to identify factors associated with effectiveness. Changes over time in erythrocyte- and iron-related parameters and erythropoiesis-stimulating agent (ESA) dose were investigated in the effective group. A total of 84 courses (77.8%) satisfied the effectiveness criteria. Compared with the effective and ineffective groups, only C-reactive protein (CRP) was significantly different (p < 0.01). ROC curve analysis with efficacy as the endpoint showed a CRP cut point value of ≤0.1 mg/dL (area under the curve, 0.69; 95% confidence interval, 0.57–0.81). The relationship between serum ferritin and hemoglobin fluctuation by reducing the ESA dose showed a positive correlation (p < 0.001). In the ESA maintenance group, the serum ferritin gradually increased and then remained constant at about 60 ng/mL. Our data suggest that patients with CRP ≤ 0.1 mg/dL may benefit from low doses of oral iron supplementation. Approximately 60 ng/mL serum ferritin may be sufficient during stable hematopoiesis.