Objectives: Necrotizing enterocolitis (NEC) is an important cause of morbidities and mortality in preterm neonates. We investigated the relationship between descending aorta (DA) blood flow pattern and the development of NEC in preterm neonates and assessed risk factors for developing NEC. Materials and Methods: This s was an observational case-control study in 62 preterm neonates at a tertiary referral neonatal intensive care unit. Clinical and echocardiographic data were collected from 28 preterm neonates with NEC (NEC group) and compared to those of 33 gestational age-matched neonates without NEC (control group). Echocardiography was done at a median (range) 5 (0-20) days in NEC group and 4 (2-31) days in control group after birth, respectively. In NEC group, NEC was diagnosed at a median (range) 10 (2-24) days after birth and echocardiography was done at a median (range) 2 (0-14) days before the diagnosis of NEC. Results: Basic clinical characteristics including gestational age, birth weight, Apgar score, the ratio of breast feeding, use of umbilical catheters and mode of invasive ventilator were similar between groups. Compared to control group, the lowest diastolic velocity of DA was significantly diminished, whereas diastolic reverse flow of DA and the ratio of diastolic reverse flow of DA to DA forward blood flow were significantly increased in NEC group. In addition, resistive index of DA, a surrogate of peripheral vascular resistance, was significantly increased in NEC group and showed positive association with development of NEC. Those parameters were also significantly different among 3 NEC subgroups according to NEC stages. Multivariate logistic regression analysis showed that increasing resistive index of DA was the only risk factor for development of NEC (Odds ratio 11.6, 95% CI 1.31–103.2, p 0.05). Conclusions: Significant hemodynamic changes of DA flow including decreased diastolic velocity, increased diastolic reverse flow along with an increase in peripheral vascular resistance were observed before development of NEC in preterm neonates. These findings may help clinicians stratify neonates at risk of developing NEC in advance and perform sophisticated clinical practices to improve outcomes in in these critically ill patients