Introduction: The recently published whole genome sequences of the two strains of H. pylori (26695 and J99) and unpublished whole genome sequence of the Korean strain 51 enabled us to perform the proteomic analyses of H. pylori. Analysis of antigenic components of H. pylori is essential for developing control strategies of H. pylori infections. In this study, the antigenecity and antigenic differences between the strains (26695, J99 and strain 51) of H. pylori were analyzed with the two dimensional electrophoresis, immunoblotting and MALDI-TOF-MS. Methods: The pH 3–10, linear IPG strips, in which whole cell lysates of H. pylori were separated by the isoelectric focusing, were applied for two dimensional electrophoresis, and IgG, IgA and IgM immunoblotting with the sera of seven H. pylori infected and three non-infected volunteers. Different antigenic spots were analyzed with MALDI-TOF-MS. Results: H. pylori showed 200 recognizable antigenic spots on IgG 2-DE immunoblot. IgA 2-DE immunoblots showed the 150 recognizable antigenic spots. IgM 2-DE immunoblots showed the 8 recognizable antigenic spots that were commonly recognized on IgG and IgA immunoblots by both H. pylori-positive and –negative sera. Among 200 antigenic spots on IgG 2-DE immunoblot, 73 spots could be identified by MALDI-TOF-MS. The identified spots represented 44 genes. The antigenic profile of H. pylori strain J99 was similar to that of H. pylori strain 51. However, H. pylori strain 26695 showed quite different pattern when compared with strain J99 and strain 51. H. pylori strain 26695 did not show 9 spots in the region of pE 4.5–5.3 and molecular weight 55–90 kDa that appeared in H.pylori strain J99 and 51. Conclusion: In conclusion, the antigenic components of H. pylori were analyzed and identified by using the immunoblot analysis employing 2-DE and the proteomic analysis, which is great helpful in the search for candidate proteins for diagnostic assays and vaccine design.