OBJECTIVE: Helicobacter pylori infections have been suggested to be associated with several extra gastric maladies, including hepatobiliary cancer (HBC). However, reports on the relationship between H. pylori infection and HBC showed variable and contrasting findings. This study aimed to address these contrasting findings and clarify the effect of H. pylori infections on HBC. Thus, we performed a systematic literature review of published related studies and a meta-analysis of eight eligible publications. METHODS: Related studies were searched in various database websites namely PubMed, ScienceDirect, Google Scholar, and Cochrane Library. Eligible studies were collated, and data were extracted. The odds ratio (OR) and 95% confidence interval (CI) were computed and interpreted using Review Manager 5.4. RESULTS: Our overall analysis showed a significant association between H. pylori infection and HBC risk. Post-outlier analysis revealed homogeneous data (I2 = 0%, p = 0.82) and significant association (OR: 2.63, 95% CI: 1.62-4.28, P < 0.0001). Subgroup analysis based on the method of diagnosis (PCR OR: 2.46, 95% CI: 1.37-4.42, P = 0.003; ELISA OR: 2.40, 95% CI = 0.99 - 5.85, P = 0.05)  showed almost similar associations and odds ratios, but only the PCR group (I2 = 0%, P = 0.72) showed homogeneity. Subgroup analysis based on specimen types revealed consistent results for liver tissue (I2 = 0%, P = 0.82) and bile (I2= 0%, P = 0.76) samples, showing low heterogeneity. In contrast, serum samples (OR: 2.40, 95% CI = 0.99 - 5.85, P = 0.05) displayed a potential but statistically nonsignificant association, while bile samples demonstrated a significant association (OR: 3.65, 95% CI: 1.56-8.52, P = 0.003). CONCLUSION: Overall, the present study suggests that H. pylori infection is associated with increased susceptibility to HBC development, with an increased effect found in bile and serum samples as specimens of choice for diagnosing H. pylori.