Lasser and colleagues examined the frequency with which clinicians prescribe drugs in violation of black box warnings for drug-drug, drug-laboratory, and drug-disease interactions and the harm associated with such prescribing. In this observational study of approximately 325 000 outpatients, approximately 7 in 1000 patients received a prescription violating a black box warning. After adjustment for confounders, receipt of medication in violation of a black box warning was more likely when patients were older than 75 years or female. The number of medications taken, number of medical problems, and site of care were also associated with violations. Fewer than 1% of patients who received a drug in violation of a black box warning had an adverse drug event as a result.