As deaths and overdoses related to opioid use have increased, physician prescribing behavior is under greater scrutiny. Prior research has shown significant variation in opioid prescribing among emergency medicine physicians, but the degree to which emergency department prescribing contributes to overall opioid prescribing remains unknown. This retrospective study used data from the Medical Expenditure Panel Survey from 1996 to 2012 and found that the quantity of opioids prescribed increased by 471% during the study period. While the percentage of opioids prescribed in the ambulatory setting increased from 71% in 1996 to 83% in 2012, the percentage of opioids prescribed in the emergency department decreased from 7.4% in 1996 to 4.4% in 2012. Based on these findings, the authors suggest that interventions designed to reduce opioid prescribing should target the outpatient setting rather than the emergency department. A past PSNet perspective discussed opioid medications and associated patient safety risks.