Helicobacter pylori infection and nonsteroidal anti-inflammatory drugs (NSAIDs) cause the majority of bleeding ulcers. Whether the presence of H. pylori infection would affect the risk of ulcers in patients taking NSAIDs is important for both theoretical and practical reasons. However, the results have been so conflicting that there is no consensus on the management of patients requiring NSAIDs who are infected with H. pylori. The controversy is largely due to the variable study design and marked heterogeneity of the study population. Studying the interaction between H. pylori and NSAIDs without considering these factors often leads to erroneous conclusions. Current evidence suggests that H. pylori contributes to an increased ulcer risk for patients who are about to start NSAID treatment, whereas NSAIDs probably account for the majority of ulcer disease in patients who are already taking long-term NSAIDs. In the light of the reduced gastric toxicity of COX-2 inhibitors, the relative importance of H. pylori in the pathogenesis of ulcers is expected to increase. Furthermore, recent evidence suggests that H. pylori contributes to ulcer bleeding associated with low-dose aspirin. Among H. pylori-positive patients with a history of ulcer bleeding who are taking low-dose aspirin, the eradication of H. pylori has been shown to be comparable to omeprazole in preventing recurrent bleeding.