Objective To summarize and analyze the effect of multiple eradicative therapy for Helicobacter pylori (Hp) infection of elderly patients and its related factors. Methods We retrospectively analysed 332 elderly patients with Hp positive,who received multiple anti-Hp eradicative therapy according to the standard of eradication. We also checked every time with C-13 breath test after stopping drug a month, and had clear follow-up results. The collected cases were calculated with the statistical rate, multiple rate compared with Pearson chi-square test. Results Within 332 elderly patients cured by first anti-Hp eradicative therapy, 211 patients were confirmed that Hp was negative with C13 breath test;121 patients still tested positive after the first treatment ,and 117 patients received the second time of eradicative therapy,89 patients were confirmed that Hp was negative with C13 breath test; Testing is still positive for 28 patients, and 16 patients received the third time of eradicative therapy, 13 patients were confirmed that Hp was negative with C13 breath test after a month. Conclusions It is necessary to eradicate Hp timely and effectively for elderly patients with Hp infection eradication indication. To adjust regimens individually with quadruple regimens, and to extend the treatment time from one week to two weeks, may be beneficial for improving the rate of eradication.