We examined prevalence of and factors associated with substance use 10 to 11 years post-9/11 among adolescents in the World Trade Center Health Registry. Logistic regression analyses showed that adolescents who witnessed a disturbing event on 9/11 were twice as likely to report ever drinking and almost three times as likely to have ever used marijuana. Among those >= 5 years of age on 9/11, fear for personal safety on 9/11 was significantly associated with having ever smoked cigarettes, ever drank, and ever used marijuana. Intervention and education for adolescents particularly focused on substance use and coping strategies may be warranted after large-scale disasters.