Objective:To analyze the impact of previous exposure to macrolide, quinolones and nitroimidazole antibiotics on eradication rate of bismuth quadruple therapy (BQT) in newly diagnosed patients with Helicobacter pylori( H. pylori). Methods:A total of 469 patients with H. pylori initially treated at the Third Hospital of Peking University from September 2017 to August 2020 were retrospectively recruited. The therapeutic regimens were BQT containing clarithromycin/levofloxacin/metronidazole recommended by Chinese guidelines. Clinical data were collected, including general demographic data, exposure history of antibiotics, CYP2C16 metabolic pattern, endoscopic diagnosis, bacterial density, H.pylori resistance, eradication results, etc. Univariate analysis, Chi-square test, Fisher exact probability test, Kruskal-Wallis H test and Logistic regression model were used as statistical methods. Results:Among different eradication therapies, univariate and multivariate analyses suggested that previous exposure to macrolides ( OR=3.37,95 %CI 1.04-10.98, P<0.05) was relevant to the decreased eradication rate of BQT containing clarithromycin. This may be due to increased resistance to clarithromycin ( OR=6.12,95 %CI 3.99-9.40, P<0.01).The previous exposure to quinolones ( OR=3.65, 95 %CI 1.27-10.49, P<0.05) was relevant to the decreased eradication rate of BQT containing levofloxacin, which was probably explained by the increased resistance to levofloxacin ( OR=2.50, 95 %CI 1.69-3.71, P<0.01). But the previous history of nitroimidazole did not impact the efficacy of BQT containing metronidazole. Conclusions:In patients newly diagnosed with H.pylori infection, the previous exposure to macrolide or quinolones antibiotics is related to lower eradiation rates of H. pylori. Although the exposure to nitroimidazole also indicates drug resistance to metronidazole, the clinical efficacy of BQT with metronidazole 400 mg four times a day is not affected.