OBJECTIVE To investigate rates of drug and alcohol use and their association with academic performance in Moroccan youth. METHODS An adapted version of the European School Project on Alcohol and Other Drugs survey was administered to 2139 10(th)-12(th) graders in 36 Moroccan public high schools. Two multiple logistic regressions were completed, one for male and one for female subjects. Grade average was used as a two-part outcome variable, and drug use was used as a four-level categorical independent variable. Parents' education levels and socioeconomic status were included as covariates. RESULTS Of the subjects, 181 girls (16%) and 390 boys (40%) reported ever having used alcohol, hashish, or psychotropic drugs. Girls who had used any of those substances in the past 30 d demonstrated an adjusted odds ratio (AOR) of 2.62 (95%CI: 1.31-5.22) of having average or below-average grades, and those with any lifetime use showed an AOR of 1.72 (95%CI: 1.07-2.77). Among the boys, use in the past 30 d was associated with an AOR of 2.08 (95%CI: 1.33-3.24) of average or below average grades, and use in the last 12 mo with an AOR of 1.74 (95%CI: 1.00-3.05). Any lifetime use among male and previous 12 mo use among female subjects were not significantly associated with academic achievement. CONCLUSIONS Among Moroccan adolescents, drug use is substantially different between boys and girls. In both genders, lower academic achievement was associated with alcohol, hashish, or psychotropic drug use in the last 30 d.