Non-steroidal anti-inflammatory drugs (NSAID), including acetylsalicylic acid, are the most commonly applied in the world, however at the same time they constitute a risk factor for gastrointestinal complications. The main mechanism of action of NSAID is based on reducing the synthesis of prostaglandins by means of inhibiting the activity of cyclooxygenase (COX), namely, of COX-1, which generates gut protective prostaglandins, and COX-2, induced at the sites of inflammation, tissue lesions and certain neoplasm. Complications caused by NSAID within the upper gut are subject to numerous studies; however those affecting the intestines are considerably less known. The complications accompanying the use of NSAID may include intestinal strictures, enteropathy with anemia and the loss of protein, macroscopically inflammatory changes as erosions and ulceration, aggravated diverticulosis, and recurrences of ulcerative colitis. During treatment with NSAID the incidence of changes within the intestine is comparable to that within the upper gut. The incidence and character of complications concerning the small and large intestines are still under investigation. Frequently, post-NSAID intestinal changes may not present any clinical signs; it is only a serious complication (haemorrhage, perforation) that becomes the first symptom. Introducing selective COX-2 inhibitors into the treatment has significantly reduced the complications within both upper and lower digestive tract; however, the knowledge of the security profile for these preparations is not yet complete.