To examine differences between heterosexual and lesbian, gay, bisexual, and questioning students' nonmedical use of prescription drugs (NMUPD). First-year university students between October 2009 and October 2013 who self-identified as heterosexual, lesbian, gay, bisexual, or questioning. Students completed questionnaires on demographic variables and NMUPD. Any NMUPD was examined, as were stimulants, anxiolytics, and painkillers. Hierarchical regression was used to examine differential NMUPD based on sexual orientation, gender, and race. For any NMUPD and painkillers, bisexual and questioning students reported higher rates of nonmedical use than heterosexual students and gay men. When compared with heterosexual females, lesbian, bisexual, and questioning females reported higher any NMUPD and nonmedical painkiller use. For stimulants and anxiolytics, bisexual students reported the highest nonmedical use, followed by gay and lesbian students. There may be particular risk for NMUPD associated with membership in marginalized groups in terms of both sexual orientation and gender.