Healthwise. Medical Reference. A. The two most common causes of peptic ulcer disease are infection with Helicobacter pylori (H. pylori) bacteria and use of nonsteroidal anti-inflammatory drugs (NSAIDs) .Although many people are infected with H. pylori bacteria, only a few of them will develop peptic ulcer disease.ealthwise. Medical Reference. A. The two most common causes of peptic ulcer disease are infection with Helicobacter pylori (H. pylori) bacteria and use of nonsteroidal anti-inflammatory drugs (NSAIDs) .