Background:Helicobacter pylori(H. pylori) remains a major cause of gastroduodenal diseases. We aimed to evaluate the burden of this infection, particularly peptic ulcer disease in Vietnamese children. Methods: We enrolled consecutive children referred for esophagogastroduodenoscopy at two tertiary children’s hospitals in Ho Chi Minh City, from October 2019 to May 2021. Children treated with proton pump inhibitors during the last two weeks or antibiotics for four weeks, and those having a previous or interventional endoscopy were excluded.H. pyloriinfection was diagnosed with either a positive culture or positive histopathology combined with a rapid urease test, or with a polymerase chain reaction of the urease gene. The study was approved by the Ethics Committee and written informed consent/assent was obtained. Results: Among 336 enrolled children aged 4–16 (mean: 9.1 ± 2.4 years; 55.4% girls),H. pyloriinfection was positive in 80%. Peptic ulcers were detected in 65 (19%), increasing with age, and 25% with anemia.cagA+strains were detected at a higher rate in children with ulcers. Conclusions: Prevalence ofH. pyloriand peptic ulcers is high among symptomatic Vietnamese children. It is crucial to have a program for early detection ofH. pylorito reduce ulcer risk and gastric cancer later.