It has been reported that H. pylori-containing cagE was associated with duodenal ulcer. The aims of the present study were to clarify the association between the cagE gene and clinical outcome and to analyze the relationship between the cagE gene and two other virulence factors--cagA and vacA--in two areas in Japan (Fukui and Okinawa) where the prevalence of duodenal ulcer and gastric cancer risk are quite different. Eighty of 81 isolates possessed the cagE gene, and all isolates possessed the cagA gene. The vacA genotype s1c/ml was a major genotype in both areas in Japan. There was no significant association between cagE, cagA status, or vacA genotype and clinical outcome. Phylogenetic analysis of the cagE gene indicated that most Japanese isolates formed a different cluster from strains isolated in the West with an association with the vacA genotype. In conclusion, the strains with cagE, cagA, and the s1c/ml genotype of vacA are predominant in Japan regardless of clinical outcome and construct a different phylogenetic cluster from those in the West.