A persistent challenge in patient safety is detecting and intervening in unsafe situations before patients are harmed. Trigger tools have been widely used in retrospective studies to identify and characterize adverse events, and this study reports on a novel use for triggers—detecting potentially harmful drug interactions during the computerized provider order entry process. Trigger alerts in a computerized provider order entry system at three hospitals (academic, community, and rural) were reviewed by a pharmacist, who then either personally made changes or contacted the prescribing physician. The triggers were developed by a multidisciplinary team involving clinicians and information technologists and were tailored to identify clinically significant medication errors. The authors found that more than 40% of the alerts required pharmacist intervention, and that over 90% of pharmacist recommendations were accepted by the prescribing physicians. Therefore, the triggers used in this study generated far fewer false-positive alerts than seen in other studies. The proliferation of false-positive warnings is a primary contributor to alert fatigue, and although this study did not directly measure this phenomenon, it is plausible that use of more tailored alerts could avert alarm fatigue.