The increasing antibiotic resistance of Helicobacter pylori poses challenges in selecting effective eradication therapies for patients with gastric cancer. This study aimed to assess the antibiotic resistance patterns of clinical H. pylori strains isolated from gastric cancer patients, to guide H. pylori eradication strategies for those with residual gastric mucosa after gastrectomy.This study enrolled 115 consecutive patients with gastric cancer who had a positive 13C urea breath test, all of whom were scheduled for gastric resection at West China Hospital of Sichuan University. Gastric mucosa samples were collected for pathological examination, H. pylori culture, and susceptibility testing using E-test and disk diffusion methods.From 115 specimens, 86 H. pylori strains were cultured (74.8% culture rate). Of the 86 patients (59 males, 27 females; median age 59, range 34-79) with successful H. pylori isolation, histopathology revealed 37 intestinal-type, 27 diffuse-type, 9 mixed-type, and 13 unclassified gastric cancers. Sixty-one patients underwent distal gastrectomy, and 25 had radical total gastrectomy. Notably, 12 patients were diagnosed at ≤45 years, including 9 females, all with signet ring cell carcinoma. Antibiotic resistance rates were rifampicin (RIF) (69.8%), metronidazole (MTZ) (75.6%), clarithromycin (CLR) (41.9%), levofloxacin (LEV) (32.6%), amoxicillin (AML) (2.3%), tetracycline (TET) (1.2%), and furazolidone (FZD) (0%).H. pylori isolates from gastric cancer patients exhibited high resistance to RIF, MTZ, CLR, and LEV, but negligible resistance to AML, FZD, and TET. Given the compromised health status and need for concurrent therapies in these patients, AML- and/or minocycline-based regimens may represent a practical and effective treatment option for H. pylori eradication in gastric cancer patients with residual gastric mucosa after distal gastrectomy, to reduce the risk of metachronous gastric cancer.© The Author(s) 2025. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.