: Iron supplementation for blood donors is a controversial concept. However, to maintain regular blood donors, as a source of blood supply, the present paradigm is not appropriate and dose not prevent harms to blood donors. Methods: A randomized, double-masked, placebo-controlled study, was conducted by enrolling 95 female regular blood donors of childbearing age (18-49 years). The participants were selected randomly (systematic random sampling) from 300 donors who donated one unit of whole blood. These individuals were randomly assigned to receive 50 mg elemental iron or placebo once daily. Each donor was scheduled for serum ferritin determination at the beginning of the study, and 28th and 56th days after donation. Adverse effects of the treatment were evaluated on 7th, 28th and 56th days. Results: After one blood donation, mean serum ferritin concentration remained largely constant in the iron group on 28th day of the treatment, (P= 0.064) whereas it was lower in the placebo group (P= 0.001). There was no significant difference between the placebo and iron group in terms of the incidence of gastrointestinal adverse effects. Conclusion: The results of the present study indicate that short-term, low dose iron supplementation replace iron loss caused by phlebotomy, protect the female regular blood donors from iron deficiency, and assist retaining this group of donors for future donation.