Background: Many neonatal intensive care units have introduced restrictive transfusion policies for preterm infants. The justification for such an approach is debatable. Objective: To systematically review the evidence from randomized controlled trials (RCTs) on the benefit to risk ratio of lower versus higher red blood cell transfusion thresholds in preterm infants. Methods: Systematic review based on an electronic literature search (09/2007) in PubMed and CENTRAL (Cochrane Library, Issue 3 2007) for RCTs on different transfusion strategies in preterm infants. Results: Seven fully published RCTs including 712 preterm infants with various gestational and postnatal ages were found to be eligible for inclusion in this systematic review. Transfusion thresholds differed between trials, as did the duration of studies, the reported outcomes and the methodological quality. The largest RCT included 451 Extremely-Low-Birth- Weight (ELBW) infants, was of high methodological quality and found no difference in reducing mortality before discharge home or survival with any of either severe retinopathy of prematurity, bronchopulmonary dysplasia or brain injury. Conclusions: Clinical and methodological heterogeneity between studies prevents firm conclusions based on the totality of available evidence. According to the results of the largest RCT, maintaining a higher hemoglobin level in ELBW infants seems to confer little clinical benefit.