In old and even middle age, there are associations between physical health and both intelligence and education. This may occur because intelligence and/or education exert effects on lifestyle choices that, in turn, affect later health. Substance use is one aspect of lifestyle choice in young adulthood that could play such a role. The effects of intelligence and/or education on substance use could be direct and environmental, or indirect due to the presence of confounding genetic and shared family influences. We used the Minnesota Twin Family Study to distinguish these effects in males and females at age 24. In contrast to prevailing expectations, there were moderately negative direct nonshared environmental effects of both IQ and education on both smoking and drinking in both males and females. That is, controlling for family background effects in the form of both genetic and shared environmental influences, both higher IQ and greater education were associated with greater alcohol and nicotine use. These effects were accounted for by alcohol and nicotine use at age 17. Our results suggest that genetic and family-culture variables confound the associations between intelligence and education and substance use in young adults, rendering them indirect. Further research is needed to understand the roles of IQ and education in alcohol and nicotine use and their relative impacts on physical health throughout the lifespan. (Contains 6 tables and 2 figures.)