Abstract: Cannabis is generally used to enhance mood (quality of life), but it is not known whether it has this effect in the medium to longer term. Little is currently known about the temporal sequence between cannabis use and the quality of life (QOL). Data are taken from a prospective longitudinal study of pregnant women recruited at their first antenatal visit in Brisbane, Australia. Offspring data from the follow-ups with 14-year-olds and 21-year-olds are used here. Indicators of QOL, happiness, and satisfaction at 14 years are considered as predictors of subsequent cannabis use. The association between cannabis use and QOL at 21 years, adjusting for prior QOL (14 years), is also examined. Socio-demographic characteristics were included as potential confounders relevant to QOL assessments. In this cohort, lower QOL in the early teenage years predicted subsequent onset of cannabis use in young adulthood. After adjustment for socio-demographic characteristics and for QOL pre-cannabis use, participants who used cannabis more frequently had a lower QOL at the 21-years follow-up. Frequent use of cannabis does not appear to enhance the user’s QOL and appears to be associated with a reduced QOL into young adulthood.