Adverse drug events (ADEs) can lead to emergency department (ED) visits and hospitalizations. Many ADEs are preventable. Incomplete information, poor understanding, and time constraints often lead to use of potentially inappropriate medications and drug-drug interactions. In an ED, physiologic changes, such as lean body mass, kidney and liver function, and susceptibility to central nervous system depressants, must be considered. High-risk medications should be reviewed and potential drug-drug interactions should be discussed and avoided when possible. Programs, such as medication therapy management, or transitional care nursing may be helpful in preventing drug-drug interactions and use of potentially inappropriate medications.