AbstractPurpose To determine the social contexts associated with the past-year substance use (multiple substances, alcohol, marijuana, and nonmedical use of prescription opioids, stimulants, and tranquilizers) among U.S. high school seniors. Methods A secondary analysis of nationally representative survey data from 10 cohorts (2002–2011) of the Monitoring the Future study, including 24,809 high school seniors. Results The social contexts associated with the past-year substance use varied considerably based on the substance used. The most prevalent location for alcohol, marijuana, and polydrug use was at a party, whereas nonmedical use of prescription stimulants, tranquilizers, and opioids was most likely to occur at home. Most types of substance use occurred in the presence of other people with the exception of nonmedical use of prescription stimulants, which was a more solitary behavior. Conclusions These exploratory findings indicate that prevention efforts may need to account for differences in social contexts between types of substances used.