Infants in a Neonatal Intensive Care Unit(NICU) may have one or multiple blood transfusions. Studies had shown that about 25% of all transfused neonates receive one unit aliquot of packed red cells. No studies have looked at the differences in outcomes between transfused once and nontransfused neonates. We compared the outcomes of these two groups of patients by a retrospective chart review of all neonates admitted to the NICU at a university medical center during a one-year period. Any neonate who had multiple transfusions, congenital heart problems, surgery, ECMO, died or was transferred to another facility before discharge was excluded. Baseline factors measured were gestational age (GA), birth weight, Apgar scores and admission hemoglobin; outcome measures assessed were length of stay, discharge hemoglobin, being discharged home on oxygen or with an apnea monitor. Three-hundred seventy-five neonates were included, 50 had single transfusions and 325 had no transfusions. Baseline GA (32.7 vs. 34.1 weeks, p=0.0001), birth weight (1955 vs. 2293 gms, p=0.0008) and admission hemoglobin (14.7 vs. 16.9 g/dl, p<0.008) differed between the groups. In bivariate analysis, patients who received a single transfusion were more likely to have a longer length of stay (23.7 vs. 11.9 days, p<0.0001), lower discharge hemoglobin(12.6 vs. 15.2 g/dl, p<0.0001), be discharged on oxygen (14% vs. 4.9%, p=0.013) and/or with an apnea monitor (36% vs. 15%, p= 0.0003). Multivariate analysis, to correct for differences in baseline characteristics, showed that a single transfusion added additional independent information to predict differences in length of stay, discharge hemoglobin and being discharged with an apnea monitor but did not add additional independent information to predict discharge home on oxygen. In this single institution retrospective analysis, neonates receiving a single transfusion are significantly younger, smaller and more anemic on admission than nontransfused infants; they are more likely to have longer hospital stays, lower discharge hemoglobin, and to use an apnea monitor on discharge. These findings suggest that neonates who receive single aliquot transfusions are a higher risk group for these outcomes, as related to their baseline characteristics.