We performed a population-based study of over 100,000 users of diclofenac, naproxen, or piroxicam to identify cases of important blood, skin, central nervous system, kidney, pancreas, or pulmonary disorders caused by these drugs. In three cases a causal relation seemed likely; one of hemolytic anemia attributed to diclofenac, one of neutropenia attributed to naproxen, and one of pancreatitis attributed to piroxicam. In 13 additional cases a causal connection seemed unlikely but could not be fully ruled out. We conclude that such illnesses are uncommonly caused by the three agents studied.