Objective. To assess the efficacy of recombinant human erythropoietin (rHuEpo) in the treatment of the anemia of prematurity. Methodology. A double-blind, placebo-controlled study was conducted on 80 preterm infants (≤32 weeks; postnatal age, 2 to 8 weeks; central hematocrit ≤35%). Patients were randomly assigned to receive subcutaneous rHuEpo (Eprex, 600 U/kg per week) or an equivalent volume of placebo, for up to 6 weeks. All patients received supplements of vitamin E (25 IU) and iron (3 mg/kg per day). The iron supplement was increased if declining serum ferritin measurements were noted. Results. Treatment and placebo groups did not differ significantly with respect to mean gestational age, birth weight hematocrit, or reticulocyte count at study entry. Fewer transfusions were administered to those receiving erythropoietin (7 compared with 21; P = .002). Compared with the placebo group, the infants receiving rHuEpo had a higher mean hematocrit (32.3 ± 4% vs 29.3 ± 6.2%; P = .014) and absolute reticulocyte count (223 ± 73 vs 124.9 ± 73 x 109/L; P < .001) at the end of the study. The mean neutrophil count was not significantly reduced at study exit (P = .8), nor at any other period during the trial in the rHuEpo group. Intercurrent events (mostly infections) were not increased in the treatment group, although there was one case of sudden infant death syndrome at age 4 months. Conclusions. Using a dose of rHuEpo of 600 U/kg per week, this study has shown a clear reduction in the requirement for blood transfusion in preterm infants.