Non-steroidal anti-inflammatory drugs (NSAIDs) are known to increase the risk of gastrointestinal injury including gastric ulcer. Topical injury under low pH environment and cyclooxygenase-1 (COX-1) inhibition resulting in gastric prostaglandin (PG) suppression are two main mechanisms of gastric damage. Topical injury can be avoided by prodrug which is activated after absorption or alter drug administration route such as suppository. But, gastric injury by PG suppression cannot be avoided even by such contrivances. Use of selective COX-2 inhibitor is another way to reduce gastric injury and certain effect is already established. However, least expected side effect of cardiovascular damage was identified by selective COX-2 inhibitor. Still NSAIDs are effective and applicable for many diseases. Numbers of prescription for aged patients are increasing. Physicians should percept the mechanism of effect and side effect of NSAIDs, and exert their best to avoid side effects of NSAIDs.