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The antibiotic resistance of Helicobacter pylori (H pylori) is steadily increasing worldwide, resulting in the low efficiency of the current therapeutic approaches for eradication. In this study, we investigated the relationship between antibiotic resistances, the year of sample collection, and the ages of the infected individuals.A total of 29,034 gastric mucosa biopsy samples were randomly collected from January 1, 2009 to December 9, 2014 in Jiaxing City, Zhejiang Province, China. An antibiotic susceptibility testing was determined using an agar-dilution method. The statistical significance was tested using the chi-squared (χ2) test.A total of 9687 strains were isolated. The resistance rate to clarithromycin, levofloxacin, and metronidazole were 17.76%, 19.66%, and 95.5%, respectively. Resistance was rare against amoxicillin, gentamicin, and furazolidone. The metronidazole resistance rate stayed at a consistently high level. In contrast, the resistance rates of clarithromycin and levofloxacin increased rapidly from 2009 to 2011, gradually decreased from 2012 to 2013, and then increased again in 2014. Although patients ages 31 to 50 and 71 to 80 years had lower infection rates of H pylori, they also had higher resistance rates to clarithromycin and levofloxacin. The highest antibiotic resistance rate was observed in patients’ ages 71 to 80 years old. Younger patients (below 30 years old) had a lower resistance to levofloxacin. Patients’ ages 51 to 60 years old may thus represent an important category for the future study of H pylori infection.Age plays a key element in H pylori resistance to clarithromycin and levofloxacin. It is therefore necessary to consider individualized therapy for the optimized treatment of H pylori-infected patients.