Supported by the Dutch Institute for Health Care Improvement (CBO), a committee consisting of rheumatologists, general practitioners, gastroenterohepatologists, hospital pharmacists and a health-economist have developed a national evidence-based guideline for the prevention of gastric damage by non-steroidal anti-inflammatory drugs (NSAIDs). The goal of the guideline is to reduce the number of gastric ulcers with perforation or bleeding as a consequence of NSAID use. It is estimated that 165 patients died as a result of these complications in the year 2000. The guideline comprises chapters on the risk factors for ulceration during NSAID use, the effectiveness and relative toxicity of different NSAIDs for the stomach, the effectiveness of various treatments meant to reduce the risk of gastro-duodenal damage, and the management of dyspeptic symptoms during NSAID use. A strategy is recommended in which prescription of NSAIDs is always preceded by an assessment of the degree to which the risk of gastric damage is increased: the most important risk factors that need to be identified are previous peptic ulcer disease, age over 70 years, and an untreated Helicobacter pylori infection associated with peptic ulcer disease. Whenever an increased risk of gastro-duodenal damage is present, the prescribing physician can choose one of three preventive strategies: addition of misoprostol, addition of a proton-pump inhibitor, or the prescription of a COX-2-selective NSAID. Provided that adequate risk assessment has been carried out, the guideline leaves it to the patient and physician to choose which of these preventive measures, all of which result in roughly equal risk reduction and costs, is the most suitable for individual situations. The use of aspirin or a coumarin derivative increases the risk; several preventive strategies are possible; the guideline discusses the situation that arises when NSAIDs are added to the treatment.