Introduction: H. pylori has been detected in patients with hepatobiliary diseases. It is currently unclear whether the H. pylori detected in hepatobiliary patients are genetically similar to those in gastro-duodenal patients. The aim of this study was to determine H. pylori vacA and cagA genotypes in Thai patients with gastro-duodenal and hepatobiliary diseases. Methodology: H. pylori DNA was extracted from samples from gastric biopsies of gastro-duodenal patients (n=100) and from bile samples of hepatobiliary patients (n=80). The vacA and cagA genotypes were performed via polymerase chain reaction (PCR) followed by DNA sequencing. Results: The vacA m1 was found in Thai hepatobiliary patients (90%) at a higher rate compared with gastro-duodenal patients (50%).The combined vacA s1a+c/m1 were mostly found in Thai gastro-duodenal and hepatobiliary patients. The cagA gene was detected in 94% of patients with gastro-duodenal diseases compared with 28.8% in those with hepatobiliary diseases (p<0.05). On the other hand, the Western type cagA was more prominent among hepatobiliary patients (100%) than gastro-duodenal patients (57.4%), and this type was grouped into same cluster with Thai gastro-duodenal patients via phylogenetic analysis. Conclusions: Based on vacA and cagA analysis, we conclude that infection with H. pylori in gastro-duodenal and hepatobiliary patients may be caused by the different H. pylori strains.