Résumé : Objective The nonmedical use of prescription drugs (NMUPD) is attracting public attention. We aimed to explore the association between sexual attraction and NMUPD among Chinese adolescents. Method A school-based survey was conducted in seven Chinese provinces, and a multi-stage stratified cluster sampling method was used in this study. A total of 150,822 students from seven Chinese provinces completed the questionnaire; the response rate was 95.93%. All data were collected between November 2014 and January 2015. Results Overall, 8.8%, 4.4%, and 2.2% of the students reported lifetime, past-year, and past-month NMUPD, respectively. Compared with heterosexual students (8.2%), sexual minority and unsure students were more likely to report lifetime NMUPD (14.4% and 10.0%, respectively; χ2 = 244.34, P < 0.001). In addition, sexual minority and unsure students were more likely to admit past-year and past-month use of NMUPD. After adjusting for social demographics and lifestyle covariates, sexual minority and unsure students were at an increased risk of lifetime NMUPD (adjusted odds ratio [AOR] = 1.68, 95% confidence interval [CI] = 1.54-1.83 and AOR = 1.33, 95% CI = 1.26-1.41, respectively). Conclusions Our study suggested that sexual minority and unsure adolescents have a higher risk of NMUPD. Moreover, our study suggested that sexual minority and unsure students are more likely to both try and continue to use prescription drugs. Further studies focusing on the mechanism of substance abuse and appropriate interventions among sexual minority and unsure adolescents are warranted.