Based on information derived from computers used by general practitioners in the United Kingdom, we identified all patients with any recorded diagnosis of a liver disorder within 90 days of a prior prescription for diclofenac, naproxen, or piroxicam, three nonsteroidal antiinflammatory drugs (NSAIDs). The follow-up cohort consisted of 102,644 persons who used one or more of these drugs. A case history was requested from the physician to provide a description of the liver disorder and its relation to NSAID exposure. One case of clinically important liver disease was likely to have been caused by a study drug and another appeared to be caused by use of numerous NSAIDs. In 10 additional patients a causal connection between a study NSAID and the liver disorder seemed unlikely but could not be fully ruled out. We conclude that serious liver disease caused by diclofenac, naproxen, or piroxicam appears to be uncommon.