Women who start using cannabis during adolescence are considerably more likely to repeatedly engage in risky sexual behaviors such as rVUS. We conclude that this relationship might not be entirely explained by a generalized predisposition to disinhibited behaviors. Reducing exposure to early life factors that increase person-specific liability to both substance use and risky sex might prevent onset of both behaviors. Furthermore, interventions that aim to create prosocial environments for female engagement, especially in women at high risk for adolescent cannabis use, may substantially attenuate the frequency of rVUS in women, a behavior with deleterious consequences for women’s health and well-being.