Aims: Secondary hyperparathyroidism (HPT) worsens anemia and may cause hyporesponsiveness to recombinant human erythropoietin therapy (r-HuEPO). To investigate the effect of parathyroidectomy (PTX) on iron homeostasis and erythropoiesis, we conducted a prospective study in chronic hemodialysis patients who underwent PTX. Methods: Thirty-two patients were enrolled in this study. Based on the increases in hemoglobin level after PTX, patients were divided into responders and nonresponders. Iron homeostasis and erythropoiesis were assessed before and 1 and 3 months after PTX, hemoglobin and parathyroid hormone levels were monitored until 6 months after PTX. Results: In the responders, increased hemoglobin levels were observed in 15 patients at 1 and 3 months after PTX (8.0 ± 0.8 g/dl vs. 9.2 ± 1.3 and 10.1 ± 0.9 g/dl, p < 0.05). The nonresponders had higher pre-PTX hemoglobin levels than the responders (10.3 ± 1.6 g/dl vs. 8.0 ± 0.8 g/dl, p < 0.05). There was no further increase in hemoglobin at 6 months compared to 3 months after PTX in both groups. In neither group did PTX affect serum ferritin, transferrin saturation and serum erythropoietin level. Serum soluble transferrin receptor (sTfR) concentration was found to be higher in responders than in nonresponders (3.32 ± 1.28 mg/l vs. 1.70 ± 0.31 mg/l, p < 0.05). Conclusions: We conclude that PTX can improve anemia in hemodialysis patients with severe hyperparathyroidism and greater resistance to r-HuEPO therapy. The reversing of anemia does not involve altering iron mobilization. Pre-PTX hemoglobin and serum sTfR levels can predict the effect of PTX on correcting anemia.