BACKGROUND: Currently, quadruple therapy is unanimously recommended as the current first-line treatment option for Helicobacter pylori (H. Pylori) eradication. However, the drug composition of quadruple therapy is very complex, and the efficacy and safety between them is not clear. AIMS: To compare the efficacy and safety of H. Pylori eradication regimens, which were recommended by the Fifth Consensus of China, by network meta-analysis. METHODS: Literature databases were used to retrieve clinical randomized controlled trials of H. Pylori eradication. Network meta-analysis was performed using BUGSnet and meta package of R software, using OR values as effect size, and SUCRA was used to rank the efficacy of interventions under each outcome. RESULTS: A total of 55 studies and 130 arms were included. The NMA analysis found that the top regimen in term of eradication rate outcome was: Rabeprazole + Bismuth + Furazolidone + Tetracycline (SUCRA, 97.5). In terms of safety outcomes: Lansoprazole + Bismuth + Amoxycillin + Clarithromycin (SUCRA, 91.97). CONCLUSIONS: The bismuth quadruple therapies recommended by the guidelines for the treatment of H. Pylori have good performance in terms of four-week eradication rate and safety outcome indicators, and due to the different resistance of antibiotics in different regional populations, rational use of drugs should be combined with local conditions.