Packed red blood cell transfusion may increase the risk of necrotizing enterocolitis in premature infants. We hypothesize that the postprandial increase in mesenteric blood flow velocity (MBFV) would not be altered by a blood transfusion in premature infants. Infants born at 25 to 32 weeks and feeding at least 60 mL/kg/d who required a transfusion were randomized within each of two weight strata to feed or not feed during the transfusion. Mean, peak systolic, and end diastolic Doppler MBFV was measured 30 minutes before and after feedings at baseline (anemic) and with the first feeding posttransfusion. Twenty-two infants (27.3 +/- 2.3 weeks' gestational age; hemoglobin [HgB] 9.3 +/- 1.3 g/dL) were studied on day of life 3 to 71 (mean 31.2 days) and a corrected gestational age of 31.8 +/- 2.9 weeks. In the entire cohort, the peak systolic ( P = 0.02) and the mean ( P = 0.01) MBFV increased in response to feeding in the anemic but not the transfused state. On subgroup analysis, only anemic infants > 1250 g ( N = 12, HgB 8.6 +/- 0.9 g/dL) had an increase in peak systolic ( P = 0.04) and mean ( P = 0.006) MBFV with feeding. In conclusion, the MBFV increases in response to feeding in anemic preterm infants > 1250 g. We speculate that the lack of response to feeding in the immediate posttransfusion state may contribute to the development of transfusion-associated necrotizing enterocolitis.