Recent studies, included using capsule endoscopy and balloon endoscopy, have revealed that nonsteroidal anti-inflammatory drugs (NSAIDs) can cause a variety of abnormalities in the intestine. Several reports show that NSAIDs included acetylsalicylic acid can induce small intestinal injuries with high prevalence in patients taken these drugs. These reports have shown that the preventive effect of proton pump inhibitors (PPIs) does not extend to the small intestine, suggesting that concomitant therapy may be required to prevent small intestinal side effects associated with NSAIDs use. Recently, several randomized controlled trials evaluated the preventive effect of mucoprotective drugs and cyclooxygenase-2 selective inhibitors against traditional NSAIDs-induced small intestinal injury. However, those studies were limited to a small number of subjects and tested short-term NSAIDs treatment. Therefore, further extensive studies are clearly required to ascertain the beneficial effect of these drugs.