AbstractBackground Simultaneous alcohol and marijuana (SAM) use raises significant concern due to the potential for additive or interactive psychopharmacological effects. However, no nationally representative studies are available that document prevalence, trends, or related factors in US youth SAM use. Methods Nationally representative cross-sectional samples of 12th grade students surveyed in the Monitoring the Future project from 1976 to 2011 provided data on SAM use. Analyses were conducted in 2012. Results In 2011, 23% of all US high school seniors reported any SAM use. Among seniors reporting any past 12-month marijuana use, 62% reported any SAM use and 13% reported SAM use most or every time they used marijuana. SAM use consistently followed trends for past 30-day alcohol use over time. SAM use showed significant variation by psychosocial and demographic characteristics and was strongly associated with higher substance use levels, but occurred across the substance use spectrum. Certain reasons for alcohol or marijuana use (to increase effects of another drug; I’m hooked) and situations of alcohol or marijuana use (park/beach, car, party) were strongly associated with SAM use. Conclusions A sizable proportion of US high school seniors reported SAM use, and it appeared to occur frequently in social use situations that could impact both the public as well as youth drug users. SAM use appears to be a complex behavior that is incidental to general substance use patterns as well as associated with (a) specific simultaneous reasons (or expectancies), and (b) heavy substance use and perceived dependence, especially on alcohol.