This study highlights the iron profile of myelodysplastic patients in the era of hepcidin and its pro-hormone, pro-hepcidin. Previous studies have focused on the anemia of chronic renal failure, thalassemia, and hemochromatosis. We determined if pro-hepcidin played a role in iron overload in patients with myelodysplasia (MDS). Thirty adult patients with MDS and 20 healthy adults (controls) were selected. Our results revealed a statistically significant difference in pro-hepcidin levels between the two tested groups (Z = 2.9, p = 0.003). There was a weak positive correlation between pro-hepcidin and hematocrit (HCT; r = 0.49, p = 0.02) in the healthy group only. Neither age, subtypes of MDS, gender, soluble transferrin receptor (sTFR) or ferritin affected the pro-hepcidin level in patients with MDS. The role of ineffective erythropoiesis in the regulation of pro-hepcidin is superior to the role of chronic blood transfusion therapy.