The effect of nonsteroidal antiinflammatory drugs (NSAIDs) on the risk of cardiovascular events remains controversial. Among NSAIDs, only low-dose aspirin exerts protective vascular effects. Low-dose aspirin has been proven effective for secondary prevention. For primary prevention, the usefulness of low-dose aspirin is debated, as illustrated by the differences in recommendations across countries. NSAIDs other than aspirin, whether COX-2 selective or nonselective, increase the risk of cardiovascular events. Among them, naproxen is associated with the smallest risk increase. In patients with a history of coronary artery disease, diclofenac seems to carry the greatest risk, but all NSAIDs should be avoided. Uncertainties persist about aspirin interactions with other NSAIDs and with proton pump inhibitors. An adverse effect of acetaminophen on the risk of cardiovascular disease cannot be completely ruled out.