Evidence suggests that lesbian and gay young adults use substances more frequently than their heterosexual peers. Based on the life course perspective, we argue that this difference may be due to the unavailability of marriage as a turning point in the lives of lesbian/gay young adults. We use data from a nationally representative sample of youth (N = 13,581, 52.4% female, 68.6% white, ages 18-26) to examine sexual orientation differences in substance use and explore whether these differences vary by romantic partnership formation in young adulthood. We find that the formation of more serious partnerships (e.g., cohabitation, marriage) is associated with less frequent substance use among heterosexual young adults, though this pattern does not hold for lesbian and gay young adults. We conclude that the partnership options available to lesbians and gay men do not provide the same health-protective benefits that marriage does for heterosexuals.