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Background: Helicobacter pylori infection is strongly associated with gastric cancer. However, there is currently no consensus on the association between H. pylori and gastric cancer prognosis. Methods: A systematic search was conducted on studies in PubMed, EMBASE, and Web of Science up to March 10, 2022. The quality of all included studies was assessed using the Newcastle-Ottawa Scale. The hazard ratio (HR) and its 95% confidence interval (95% CI) were extracted to analyze the association between H. pylori infection and prognosis of gastric cancer. In addition, subgroup analysis and publication bias were performed. Results: A total of 21 studies were involved. The pooled HR was 0.67 (95% CI, 0.56–0.79) for overall survival (OS) in H. pylori-positive patients, with the control (HR = 1) being the H. pylori-negative group. In the subgroup analysis, the pooled HR was 0.38 (95% CI, 0.24–0.59) for OS in H. pylori-positive patients who received surgery combined with chemotherapy. The pooled HR for disease-free survival was 0.74 (95% CI, 0.63–0.8) and 0.41 (95% CI, 0.26–0.65) in patients who received surgery combined with chemotherapy. Conclusion: H. pylori-positive gastric cancer patients have a better overall prognosis than H. pylori-negative patients. H. pylori infection has improved the prognosis of patients undergoing surgery or chemotherapy, among which the improvement was most obvious in patients undergoing surgery combined with chemotherapy.