There is a selected group of infants with Congenital Heart Diseases (CHD) characterized by reduced pulmonary blood flow. In them, arterial oxygen saturation levels (O2Sat) is persistently low (usually around 80%) until complete recovery or surgical repair. These infants require high Hemoglobin(Hb) concentrations and Hematocrit (Hct) levels to preserve adequate arterial content and delivery of O2. They frequently need blood transfusions to maintain Hct levels of at least 55%. Human EPO has been used clinically in infants with anemia of prematurity and bronchopulmonary dysplasia, but there is no clinical experience with its use in newborns with cyanotic CHD. In this observational pilot study we evaluated whether early use of EPO in these infants blunts the physiological descent of Hb that occurs during the first 12 weeks after birth and reduces the need for transfusions. We present preliminary data in 10 infants. Six of them had Pulmonary Stenosis (PS) and poorly compliant right ventricle. They all showed significant improvement in O2Sat after valvular ballon dilation, but O2Sat remained below 86%. The other 4 infants had complex CHD not amenable to complete primary repair during the early neonatal period (i.e. AV canal. TGA with pulmonary stenosis). Infants were included in the study if the Hct was in progressive descent and it was<50%, regardless of previous blood transfusions. EPO was started at a mean age of 2 weeks at a dose of 250u/kg S.C. three times a week while in hospital and continued for at least two weeks after discharge. All patients received iron at a dose of 6mg/kg/day while on EPO. As outpatients, Hct and Reticulocyte (Ret) counts were measured every 7-10 days and more frequently when in hospital. Response to EPO was evaluated by Hb. Hct and Ret counts and need for transfusions. The 10 infants showed an increase in their Ret counts and no infant showed a decrease in the Hct and Hb levels. None required transfusions to maintain Hct>45%. While on EPO, two patients developed Hct>60%, though post-discharge follow-up and frequency of lab test was inappropiate. We conclude that the early use of EPO abolishes the physiologic descent of Hb and Hct in these infants. These findings may render EPO useful, safe and cost-efficient for the adjuvant management of patients with CHD and reduced pulmonary flow until the condition resolves completely, either spontaneously (i.e. improved compliance of right ventricle in cases of PS), or surgically.