The safety benefit of computerized provider order entry systems rests in large part on the ability to provide decision support—for example, alerts that warn clinicians about potential drug–drug interactions. However, this study of more than 200,000 alerts generated by a commercial outpatient electronic prescribing system found that clinicians rejected the vast majority of alerts, even those representing "high-severity" drug interactions. The study also found evidence of "alert fatigue," where heavier users of the system were more likely to reject drug interaction warnings. This phenomenon has been previously documented as one of several types of unintended consequences of computerized order entry. Improvements in the decision support system, such as tiering alerts, have been associated with increased acceptance of warnings.