The widespread of eradication therapy for H. pylori has lead to an increase in antibiotic resistant strains. The combination of a proton pump inhibitor, amoxycillin and clarithromycin (PPI/AC) has been one of the most popular regimens and has shown satisfactory results. Clarithromycin (CAM)-resistance of H. pylori is a clinical problem because it reduces the efficacy of PPI/AC regimen. We investigated the rate of acquisition of H. pylori resistance against CAM before triple therapy. The rate of CAM-resistant strains was 0% in 1985, 14.6% in 1996-99, 21.2% in 2001-04, and 24.1% in 2005-08, respectively. Tokyo H. pylori Study Group consisting of eleven institutions assessed the eradication rate of PPI/AC regimen from 2001 to 2008 in Tokyo metropolitan area. Intension-to-treat based eradication rate for PPI/AC regimen was decreased gradually from 70% to 60% level. The reduction in eradication rate of H. pylori consisting of PPI/AC was recognized. Furthermore, when the increase in CAM-resistant strains results in a decrease in eradication rate for H. pylori, new alternative first-line treatment combination should be considered in Japan.