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Abstract Objectives Peptic ulcer disease (PUD), affects adults and children, with Helicobacter pylori ( H. pylori ) infection being the most frequent cause. Diagnosis requires an upper gastrointestinal endoscopy (UGE) and invasive tests. However, besides H. pylori , risk factors for PUD in children remain unclear. The aim of this study is to investigate pediatric PUD's epidemiology, etiology, and associated risk factors. Methods A retrospective case‐control study included children aged 1 month to 17 years presenting PUD, defined as presence of ulceration/erosion of the gastric/duodenal mucosa, and two controls per case. UGE's were performed between 2016 and 2022 in a pediatric center. Diagnosis of H. pylori was based on culture and histology of gastric biopsies. Results Among 2355 eligible children, 335 with PUD (14.2%) and 670 controls were included. The median age was 9.9 years (IQR: 6.1–13.1). The main indications for endoscopy were dyspepsia (38.7%) and chronic abdominal pain (15.5%). H. pylori infection was more frequent in cases than controls (35.7% vs. 17.2%, p < 0.001). Independent risk factors for PUD included age ≥ 11 years (OR 1.83, 95% CI: 1.21–2.75; p = 0.004), gastrointestinal bleeding (OR 3.18, 95% CI: 1.15–8.82; p = 0.026), and concomitant medication use (OR 6.93, 95% CI: 3.51–13.7; p < 0.001). Epigastric tenderness, systemic diseases, and a family history of PUD or H. pylori infection were associated with PUD only in univariable analysis. Conclusion Older age, concomitant medications, and H . pylori infection are risk factors for pediatric PUD. In a tertiary center, PUD remains a frequent and clinically relevant diagnosis among children undergoing UGE.