A retrospective study investigated the risk factors of acute gastrointestinal injury (AGI) in 62 pediatric patients treated with ECMO in hospitals in Gansu and Shaanxi since January 2019. Patients were divided into significant AGI (grade II or higher, 28 patients, 45.16%) and insignificant AGI (no AGI or grade I, 34 patients, 54.84%). Univariate analysis showed significant differences between groups in ECMO duration, pre-ECMO blood lactate levels, vasopressor-inotropic score (VIS), time to start enteral nutrition, and pre-ECMO proton pump inhibitor (PPI) use (P < 0.05). Binary logistic regression identified prolonged ECMO duration, elevated pre-ECMO lactate levels, and pre-ECMO PPI use as independent risk factors. Early initiation of enteral nutrition within 48 hours was a protective factor. The incidence of significant AGI in children on ECMO is high.