A great deal of research on adolescent suicidal behavior has focused on depression and alcohol use. Major depression and mood disorders have been shown consistently to be the psychiatric disorders most highly associated with attempted suicide in adolescence. However, less attention has been given to illegal drug use, specifically polydrug use. The Objective of this study is to determine the association between suicidal attempts and polydrug use in a nationally representative sample of secondary school students in Puerto Rico. Consulta Juvenil X is a monitoring program that Aims to study the prevalence of substance use and violent behavior as well as the risk factors associated with those practices. The survey was conducted during the 2018-20 academic year. The study utilizes a self-administered questionnaire. Use of two or more substances (tobacco, marijuana, cocaine, heroin, or amphetamines) in addition to using alcohol was defined as polydrug use. The sample included 4668 (54%) females and 3977 (46%) males. Half of the sample was between seventh and ninth grade with a median age of 15 years old. The prevalence of polydrug use in the public and private schools participating in the study was 9.4% and the suicide attempts was 7.6%. Multiple logistics regression analyses revealed that students who use multiple substances during the last year were significantly more likely to report suicide attempts after controlling for depression symptoms and other sociodemographic variables (OR=3.07; 95%CI: 2.53-3.72). Adolescents who used three or more substances (95%CI=7.00-10.84) were 8.7 times more likely to attempt suicide than those who did not use drugs. Findings of this study suggest that adolescents who use multiple substances seem to be at higher risk for suicide behaviors. Understanding who is most likely to report polydrug use is important in developing interventions to prevent suicidal attempts.