IntroductionNecrotizing enterocolitis (NEC) is a serious intestinal condition characterized by ischemic necrosis of the intestinal mucosa, inflammation, and invasion by gas-forming organisms, posing a significant threat to neonatal health. Necrotizing enterocolitis remains a significant cause of neonatal morbidity and mortality, particularly in developing countries. Due to limited research conducted in Ethiopia and the study area, there is a lack of information regarding the risk factors associated with necrotizing enterocolitis. Therefore, the goal of this study is to fill the aforementioned gap.ObjectiveThis study aims to identify the risk factors of necrotizing enterocolitis among neonates admitted to the neonatal intensive care unit (NICU) at selected general and referral hospitals in southern Ethiopia in the year 2023.Methods and materialsA facility-based unmatched case–control study was conducted. All neonates admitted to the NICU and diagnosed with necrotizing enterocolitis by the attending physician during the data collection period were considered as cases, whereas neonates admitted to the NICU but not diagnosed with necrotizing enterocolitis during the data collection period were considered as controls. Data were collected through face-to-face interviews and record reviews using the Kobo toolbox platform. The binary logistic regression method was used to determine the relationship between a dependent variable and independent variables. Finally, a p-value of < 0.05 was considered statistically significant.ResultsThis study included 111 cases and 332 controls. Normal BMI [AOR = 0.11, 95% CI: (0.02, 0.58)], history of khat chewing [AOR = 4.21, 95% CI: (1.96, 9.06)], term gestation [AOR = 0.06, 95% CI: (0.01, 0.18)], history of cigarette smoking [AOR = 2.86, 95% CI: (1.14, 7.14)], length of hospital stay [AOR = 3.3, 95% CI: (1.43, 7.67)], and premature rupture of membrane [AOR = 3.51, 95% CI: (1.77, 6.98)] were significantly associated with NEC.ConclusionThe study identified several risk factors for necrotizing enterocolitis, including body mass index, history of khat chewing, gestational age, history of cigarette smoking, length of hospital stays, and premature rupture of membrane. Therefore, healthcare providers should be aware of these risk factors to identify newborns at high risk and implement preventive measures.