Non-steroidal anti-inflammatory drug use is associated with gastrointestinal side-effects including complications such as bleeding and perforation, which occur in 1-2% of patients after 6-12 months of therapy. A high level of non-prescription non-steroidal anti-inflammatory drug use is observed among those presenting complications. More common side-effects are symptomatic gastro-duodenal ulcers (annual incidence of 4-8%) and dyspepsia (25-50%). Low-dose aspirin use is also associated with an increased risk of upper gastrointestinal bleeding, but the increase is about 3 times lower than that found with common non-steroidal anti-inflammatory drugs. Recent studies suggest that the risk of bleeding in patients taking preferential cyclooxygenase-II inhibitors (e.g. nimesulide) is similar to that in patients taking non-selective non-steroidal anti-inflammatory drugs. Epidemiological studies have also shown that nitric oxide donors and antisecretory drugs reduce the risk of upper gastrointestinal bleeding both in non-steroidal anti-inflammatory drug and low-dose aspirin users.