Gastrointestinal (GI) toxicity is a major limiting factor in the use of nonsteroidal anti-inflammatory drugs (NSAIDs). Because of the widespread use of these medications, the morbidity and costs associated with GI complications of NSAID use are significant. On the other hand, the costs of providing prophylactic cotherapy to all patients to prevent NSAID-induced ulcers and bleeding are prohibitive. The presence of specific risk factors (advanced age, prior peptic ulcer disease and bleeding, high NSAID doses and concomitant therapy with corticosteroids or anticoagulants) identifies patients who are most likely to have a GI complication. The recognition of these risks in specific patients may influence therapeutic decisions that could decrease the morbidity and costs of NSAID therapy.