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Iron deficiency represents a risk to donor health and the blood supply. Efficacy trials indicate that postdonation iron replacement improves iron stores but they do not account for complexities of implementation in the routine collection context. We therefore conducted two prospective feasibility studies in Australian donor centers.In both studies we recruited female donors between 18 and 45 years who had made at least one donation in the previous 12 months. In READ (replacement advice), female donors were given a recommendation to self-procure postdonation iron. In DIRECT (donor iron replacement), donors were provided with a course of iron supplements. Donors could return to donate at their discretion and were surveyed after the recruitment visit and again toward the end of the 13-month follow-up. Donor uptake, adverse effects, effectiveness in maintaining iron stores, and workflow impact were assessed.We recruited 1404 (70.9% of invited) donors to READ and 768 (53.2% of invited) to DIRECT. READ and DIRECT extended predonation interviews by 1 and 5 minutes, respectively. Among participants, 44 and 88% took iron in READ and DIRECT, respectively. Adverse effects were common but usually mild. READ failed to maintain iron stores in the population, but was effective in donors who consumed more than 75% of the recommended dose. DIRECT was effective in preventing declines in ferritin concentration.Trade-offs between cost, complexity, uptake, and effectiveness must be considered in the implementation of postdonation iron supplementation.