We hypothesized that adolescent cannabis use would be associated with an increased likelihood of rVUS and that this association would be partly due to shared familial influences but would also persist after such shared familial influences were accounted for. In a large cross-sectional sample of 2,784 sexually active female twins aged 18 to 27 years, we examine the extent to which genetic and environmental factors contribute to the association between first cannabis use prior to age 17 and repeated (≥3 times) voluntary unprotected sex (rVUS). Analyses were further conducted within discordant pairs of twins, specifically in the subset of MZ twins discordant for adolescent cannabis use (Npairs= 115) to examine whether the association persisted after accounting for genetic similarity and familial environment. Finally, classical twin modeling was also used to quantify the extent to which genetic and environmental factors contributed to variance in and covariance between adolescent cannabis use and rVUS.