This international study investigates factors underlying international variations in rates of youth drug use among representative samples of 15-year-olds in five cities (Bremen, n = 871; Dublin, n = 983; Groningen, n = 487; Newcastle upon Tyne, n = 880; Rome, n = 666). It reveals a higher level of drug use in English-speaking compared to continental populations. Drug use was associated with peer, family and individual factors. Logistic regression showed that family structure and sport were associated with lower rates and delinquent behaviour with higher rates of drug use in all cities and among males and females. Among males, city of residence also independently predicted drug use. The effect of traditional families and studiousness in reducing drug use was most evident for male drug use in low-use cities: higher rates of use in English-speaking cities appear partially due to the drug use of low-risk males.