After discovery of H. pylori, management of peptic ulcer disease (PUD) is getting much easier. However, four thousands a year still died caused by this disease in Japan. Ten to twenty percent of the non-NSAIDs ulcer could be expected to remain after complete eradication of H. pylori; The number could be still 100,000-200,000 a year in Japan. Furthermore, NSAIDs ulcer would not decrease in number in the post-H. pylori era. Recurrence of ulcer is related to the quality of ulcer healing. Deficiency of prostaglandins(PG) in the mucosa is another main reason than H. pylori infection of poor quality of ulcer healing. Therefore, a PG analogue may be a most reasonable tool for treatment of H. pylori-negative PUD including NSAIDs ulcer, but is often poorly tolerated because of diarrhea and abdominal pain. The mucosal damage caused by NSAIDs is also gastric acid-dependent and so, an H2-receptor antagonist is to some extent effective although the efficacy is far behind of that with a PG-analogue. Recently, a proton-pump inhibitor has been reported to exert the same effect as a PG-analogue in healing of gastroduodenal mucosal damage caused by NSAIDs and the superior effect in preventing recurrence of the damage with better tolerance. This results suggest that strong acid inhibition is highly effective for such damage. Whether such strong acid inhibition causes disturbance of absorption of NSAIDs is not clear, which might result in poor antiinflammatory effect. Elderly patients often have tendency of constipation and less possibility of pregnancy. Therefore, a PG-analogue may be not only safe but also more favorable for such patients.