The use of multiple substances heightens the risk of overdose. Multiple substances, including alcohol, are commonly found among people who experience overdose-related mortality. However, the associations between alcohol use and the use of a range of other substances are often not assessed. Therefore, this study examines the associations between drinking patterns (e.g., binge drinking) and other substance use in the U.S., the concurrent use of alcohol and prescription drug misuse, and how other substance use varies by binge-drinking frequency.