Nonsteroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori infection are the two major causes of peptic ulcers. At present, H. pylori eradication is widely recommended as the most effective treatment for preventing the recurrence of peptic ulcer. In Japan, the first-line regimen for H. pylori eradication, which consists of a proton pump inhibitors (PPI), amoxicillin, and clarithromycin (CAM), was approved in December 2000. However, the number of CAM-resistant strains causing eradication failure by triple therapy including CAM has been increasing. Previous studies have demonstrated that both misoprostol and PPIs are effective for preventing and curing NSAID-associated mucosal injuries. Proton-pump inhibitors have been reported to be better tolerated than misoprostol. In addition, histamine-H2 receptor antagonists (H2RA), when administered at high doses, have preventive effects. However, Japanese patients are expected that not high-dose but even standard-dose H2RAs are effective, because Japanese originally intend to be lower acidity than Westernaers, and have often severe corpus atrophy. For users of NSAIDs, H. pylori infection may additively or synergistically increase the risk of peptic ulcers or serious ulcer complications. H. pylori eradication has been shown to substantially decrease the recurrence rate of peptic ulcers in new NSAID users, but the efficacy in patients with chronic NSAID ulcers is controversial.