Genotyping of 74 Irish Helicobacter pylori isolates was performed at four different loci (vacA signal sequence and mid-region, insertion-deletion polymorphisms at the 3' end of the cag pathogenicity island, and cagA). The predominant vacA alleles and insertion-deletion motifs suggest an ancestral relationship between Irish isolates and either specific East Asian or Northern European strains. In addition, fluorescent amplified fragment length polymorphism-PCR genotyping and phylogenetic analysis of 32 representative Irish H. pylori isolates and 22 isolates from four different continents demonstrated that the Irish H. pylori isolates examined were weakly clonal and showed some association with both European and Asian isolates. These three genotyping techniques show that Irish H. pylori isolates have distinctive features that may have evolved in this insular European population.