The association of ecstasy (3, 4-methylenedioxymethamphetamine, MDMA) use with low academic achievement was examined in two nationally representative surveys of adolescents. We tested whether associations with low academic achievement were of similar magnitude or of stronger magnitude for ecstasy versus marijuana use (without ecstasy use), alcohol/tobacco use (without other drug use) and non-drug use in adolescence. Data from the adolescents in the 2002-2005 National Survey of Drug Use and Health (NSDUH, n=65,294) and from the 2001-2003 Youth Risk Behavior Survey (YRBS, n=27,592) were analyzed via weighted logistic regression models. Ecstasy, marijuana, and alcohol/tobacco use were associated with moderate and low academic achievement among adolescents in both surveys. Moreover, ecstasy was more strongly associated with low academic achievement and reporting that school gave no grades than alcohol/tobacco in both samples and than marijuana (NSDUH sample only). Prevention programs should inform adolescents that ecstasy use might impair their academic achievement.