Abstract. AIM: To determine risk or protective factors for the development of necrotizing enterocolitis in very low birth weight infants. METHODS: This retrospective case-control study was conducted at La Paz University Hospital including infants with a birth weight of <1500 g for three years. Cases with confirmed diagnosis of necrotizing enterocolitis were evaluated; each one was paired with a control infant of the same gestational age. Statistical analysis included unadjusted and multivariable analyses. RESULTS: A total of 576 very low birth weight infants were admitted; of them 30 infants (5.2%) developed necrotizing enterocolitis. The main clinical and demographic characteristics did not differ between the two groups. The frequency of infants transfused with packed red blood cells was similar in cases (63%) and control patients (77%). However, a greater number of transfusions increased the odds of necrotizing enterocolitis [OR 1.5, 95%CI (1.01 to 2.24)]. CONCLUSIONS: A greater number of transfusions of packed red blood cells are associated with an increased risk of necrotizing enterocolitis in very low birth weight infants. The other analyzed variables in this study do not identify the infants at risk. Caution is advocated in using transfusions in newborns.