Background: Bowel perforation is a severe complication in neonates with Hirschsprung disease (HD), particularly during the neonatal period. Identifying risk factors may aid in early detection and intervention. Methods: We retrospectively analyzed the clinical data of 300 neonates diagnosed with HD at our hospital from 2007 to 2024. The patients were divided into bowel perforation and non-perforation groups based on whether they developed bowel perforation during the neonatal period. The clinical characteristics of both groups were compared. Univariate and multivariate logistic regression analyses were performed to identify the associated risk factors, including general information, clinical symptoms, examination results, and birth history. Results: A total of 300 neonates with HD were included in this study, with a bowel perforation rate of 6.0% (18/300). The sites of perforation were the sigmoid colon (44.4%, 8/18), descending colon (27.8%, 5/18), ascending colon (11.1%, 2/18), terminal ileum (11.1%, 2/18), and transverse colon (5.6%, 1/18). The results of univariate and multivariate logistic regression analyses revealed that age at admission < 5 days, CRP > 20.5 mg/L, and radiographic findings of intestinal wall pneumatosis were independent risk factors for bowel perforation in neonates with HD, with OR (95% CI) of 4.709 (1.187, 18.684), 35.185 (9.394, 131.782), and 9.667 (2.264, 41.278), respectively. Conclusion: The incidence of bowel perforation in neonates with Hirschsprung disease is 6.0%. Bowel perforation in neonates with HD is associated with early age at admission, elevated CRP, and intestinal wall pneumatosis. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2025.