<h3>Background and aims</h3> <i>Helicobacter pylori</i> colonises the stomach in half of all humans, and is the principal cause of gastric cancer, the second leading cause of cancer death worldwide. While gastric cancer rates correlate with <i>H pylori</i> prevalence in some areas, there are regions where infection is nearly universal, but rates of gastric cancer are low. In the case of Colombia, there is a 25-fold increase in gastric cancer rate in the Andean mountain (high risk) region compared to the coastal (low risk) region, despite similarly high (∼90%) prevalence of <i>H pylori</i> in the two locations. Our aim was to investigate the ancestral origin of <i>H pylori</i> strains isolated from subjects in these high- and low-risk regions and to determine whether this is a predictive determinant of precancerous lesions. <h3>Methods</h3> Multi-locus sequence typing was used to investigate phylogeographic origins of infecting <i>H pylori</i> strains isolated from subjects in the Pacific coast and Andes Mountains in the state of Nariño, Colombia. We analysed 64 subjects infected with <i>cagA⁺ vacA</i> s1m1 strains. Gastric biopsy slides from each individual were scored for histological lesions and evaluated for DNA damage by immunohistochemistry. <h3>Results</h3> We show that strains from the high-risk region were all of European phylogeographic origin, whereas those from the low risk region were of either European (34%) or African origin (66%). European strain origin was strongly predictive of increased premalignant histological lesions and epithelial DNA damage, even in the low-risk region; African strain origin was associated with reduced severity of these parameters. <h3>Conclusion</h3> The phylogeographic origin of <i>H pylori</i> strains provides an explanation for geographic differences in cancer risk deriving from this infection.