Background <p>This study aimed to evaluate the diagnostic and therapeutic utility of ultrathin colonoscopy for lower gastrointestinal disorders in neonates, including extremely preterm infants and to describe the associated clinical and etiological spectrum.</p> Methods <p>We conducted a retrospective analysis of 15 neonates who underwent ultrathin colonoscopy at Tangdu Hospital (March 2018 to February 2026). Data on patient characteristics, clinical presentation, endoscopic findings, diagnostic yield (defined as the proportion of cases in which an etiologic diagnosis was established based on endoscopic and/or histopathologic findings.), and therapeutic outcomes were analyzed.</p> Results <p>The cohort included 15 neonates (53.3% preterm), with one extreme case of 26⁺³ weeks’ gestation and 740 g birth weight. The most common symptom was abdominal distension (13/15, 86.7%). All procedures were completed safely without complications. Abnormal endoscopic findings were observed in 13 cases (86.7%), leading to definitive diagnoses: meconium ileus (<i>n</i> = 5), allergic proctocolitis (<i>n</i> = 4), necrotizing enterocolitis (<i>n</i> = 2), very early-onset inflammatory bowel disease (<i>n</i> = 1), and eosinophilic colitis (<i>n</i> = 1). Two examinations were normal.</p> Conclusion <p>Ultrathin colonoscopy in neonates appears feasible, with a preliminary safety profile in this small, selected cohort from a single-center retrospective feasibility study, especially for non-emergent symptoms. It facilitates early etiological diagnosis and allows timely endoscopic intervention, however, larger prospective studies are warranted to confirm these preliminary observations.</p> Impact <p><UnorderedList Mark="Bullet"> <ItemContent> <p>This study demonstrates the safety and feasibility of ultrathin colonoscopy for both diagnosis and therapeutic intervention in critically ill neonates, including an extremely preterm infant with a gestational age of only 26⁺³ weeks and a birth weight of 740 g.</p> </ItemContent> <ItemContent> <p>Ultrathin colonoscopy achieved a high diagnostic yield (86.7%) for neonatal lower gastrointestinal diseases and enabled immediate minimally invasive treatment, successfully avoiding surgery in meconium ileus.</p> </ItemContent> <ItemContent> <p>The application of this technique provides a new, less invasive diagnostic-therapeutic pathway. It can serve as a minimally invasive adjunct for non-surgical management of uncomplicated meconium ileus, reducing unnecessary surgical risks in neonates.</p> </ItemContent> </UnorderedList></p>