The administration of nonsteroidal anti-inflammatory drugs (NSAIDs) is frequently associated with injury to the gastroduodenal mucosa and leads in approximately 1.5% of patients to severe complications such as haemorrhage or perforation. The risk of serious upper GI complications is increased in patients > 65 years with a previous history of peptic ulcer disease or gastrointestinal haemorrhage, concomitant steroid use and significant cardiovascular comorbidity. Previous studies have shown that misoprostol is effective in reducing the incidence of gastric and duodenal ulcers as well as serious gastrointestinal complications. Recently, four large clinical trials have demonstrated that omeprazole is effective in preventing and treating NSAID-induced ulcers. Omeprazole when compared to misoprostol was equally effective in preventing gastric ulcers and more effective in duodenal ulcers. For treatment of gastric and duodenal ulcers, omeprazole was more effective than misoprostol and ranitidin. Prophylaxis of NSAID-induced ulcers should be administered in all patients with several risk factors for serious gastrointestinal complications.