Objective To analyze the infection and drug resistance of Helicobacter pylori (Hp) in outpatients in Wuxi, Jiangsu province, and to explore the strategy of rational use of antibiotics. Methods The clinical data of children who underwent gastroscopy in gastroenterology outpatient department due to upper gastrointestinal symptoms from December 2018 to July 2021 were retrospectively analyzed. Results Gastric antral mucosa samples were collected from 716 children, including 392 boys and 324 girls. The median age was 11.0 (9.0-13.0) years, and there were 454 children ≤12 years old and 262 children >12 years old. Hp culture was positive in 260 children (36.3%), including 132 boys and 128 girls. There were 148 children ≤12 years old and 112 children >12 years old. The positive rate of Hp in children >12 years old (42.7%) was significantly higher than that in children ≤12 years old (32.6%), and the difference was statistically significant (P<0.05). The results of drug susceptibility test of 260 Hp strains showed that 10.4% (27/260) of the strains were sensitive to all six antimicrobial agents. The drug resistance rates of metronidazole, clarithromycin and leofloxacin were 75.4% (196/260), 37.7% (98/260) and 20.8% (54/260), respectively. No strains resistant to furazolidone, amoxicillin and tetracycline were found. Seventy-six patients were resistant to two antimicrobial agents, including 45 patients with dual resistance to clarithromycin and metronidazole, 11 to clarithromycin and levofloxacin, and 20 to metronidazole and levofloxacin. Nineteen children were resistant to clarithromycin, metronidazole and levofloxacin. Conclusions The positive rate of Hp culture in children of Wuxi region increased significantly with age. The drug resistance rate of Hp to metronidazole is very high. Metronidazole should be avoided in empirical treatment, and tetracycline and furazolidone can be considered to replace metronidazole.