This study was conducted using a trigger tool method in which all cases of naloxone administration in the emergency department were reviewed. Causes of iatrogenic opioid overdose included patient factors such as comorbid conditions, inappropriate prescribing practices such as coadministration of multiple opioid medications, and systems problems including suboptimal handoffs and lack of pharmacy oversight. These results clearly demonstrate the need for multimodal interventions that address the varied factors that contribute to opioid overdose in the emergency department. A recent AHRQ WebM&M commentary describes best practices for opioid prescribing.