OBJECTIVE To determine if infants with very low birth weight who receive packed red blood cell (PRBC) transfusions have increased odds of developing necrotizing enterocolitis (NEC), to determine the rate of NEC after PRBC transfusion, and to characterize the blood transfused preceding the onset of NEC. METHODS A retrospective cohort design was used. The study population included infants with a birth weight of <1500 g who were from a single center. NEC after transfusion was defined as NEC that occurred in the 48 hours after initiation of PRBC transfusion. Statistical analysis included unadjusted and multivariable analyses. RESULTS The study sample included 2311 infants. A total of 122 infants (5.3%) developed NEC, and 33 (27%) of 122 NEC cases occurred after transfusion. NEC occurred after 33 (0.5%) of 6484 [corrected] transfusions. Infants who received a transfusion had increased adjusted odds (odds ratio: 2.3 [95% confidence interval: 1.2-4.2]) of developing NEC compared with infants who did not receive a transfusion. PRBCs transfused before NEC were predominantly (83%) from male donors and were a median of 5 days old. CONCLUSIONS In our study sample, PRBC transfusion was associated with increased odds of NEC. The rate of NEC after transfusion was 1.4%. From our data we could not determine if PRBC transfusions were part of the causal pathway for NEC or were indicative of other factors that may be causal for NEC.