Objective: This study aimed to explore the potential causal relationship between Helicobacter pylori (HP) infection and esophageal cancer (EC). We employed traditional two-sample Mendelian randomization (MR) methods, combined with Bayesian-weighted MR and linkage disequilibrium score regression (LDSC), and conducted a comprehensive meta-analysis on controversial findings to strengthen the evidence base. Methods: The analysis incorporated genome-wide association study (GWAS) data with HP infection as the exposure and EC as the outcome. We utilized a variety of MR methods, including inverse-variance weighted analysis, weighted median, MR-Egger, Simple mode, and Weighted mode to investigate the association between HP and EC. Additionally, Bayesian-weighted MR was introduced and results were corrected using the false discovery rate (FDR) to enhance precision. The study also involved outlier detection, heterogeneity testing, sensitivity analysis, pleiotropy assessment, and the removal of single nucleotide polymorphisms (SNPs) potentially affected by confounding factors. For results that were particularly contentious, a meta-analysis was performed to provide a broader perspective. Potential reverse causation was assessed using Steiger testing and reverse MR. Furthermore, LDSC was utilized to evaluate the genetic correlation between HP and EC. Results: The comprehensive analyses showed that both traditional two-sample MR and Bayesian-weighted MR after FDR correction indicated no statistically significant causal relationship between HP and EC（P>0.05）. No pleiotropy was evident（P>0.05）, and the robustness of the results was confirmed by the leave-one-out test. However, genetic correlation analyses of anti-Helicobacter pylori IgG serum positivity and Helicobacter pylori GroEL antibody levels suggested a potential genetic link with esophageal adenocarcinoma（P<0.05）. Conclusion: Despite the use of advanced statistical methodologies, the current evidence is insufficient to support a definitive causal relationship between HP and EC. This finding underscores the need for larger-scale GWAS data and more detailed subtype-specific analyses to further explore the relationship between these two conditions. Future research should include a broader range of populations and geographical areas to enhance the generalizability and applicability of findings, while also investigating the specific impacts of different HP strains and possible biological mechanisms, providing stronger scientific support for the prevention and treatment of esophageal cancer.