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AIM -- Previous studies of the association between polydrug use and other risk behaviours have generally been limited to specific substances and a small number of behaviours. The aim of this study is to obtain better insight into polydrug use (comprising legal and illegal substances: tobacco, alcohol, tranquillisers/sedatives, cannabis. and other illegal drugs) and its association with co-occurring problem behaviours drawn from various broad domains (sexual, aggressive, delinquent, school achievement, relationships) among European adolescents. METHODS -- Data were obtained from 101.401 16-year-old students from 35 European countries participating in the 2011 ESPAD survey. Associations between polydrug use and other problem behaviours were examined by multinomial and binary logistic regression analyses. RESULTS -- Tranquillisers/sedatives appeared among the commonest combinations in the polydrug use pattern, especially for females. A strong trend was found between levels of involvement with polydrug use and other problem behaviours for both genders. The highest associations with polydrug use were for problems with the police, risky sexual behaviour and skipping school. Gender differences showed higher prevalences among boys than girls of problem behaviours of aggressive, antisocial type, while girls prevailed over boys in relationship problems. CONCLUSION -- An incremental relationship exists between the level of involvement with polydrug use and the co-occurrence of problem behaviours. Preventative interventions should consider the misuse of tranquillisers/sedatives within the context of polydrug use by adolescents and expand their target groups towards multiple problem behaviours. KEYWORDS - polydrug use. adolescents. ESPAD, problem behaviours [ABSTRACT FROM AUTHOR]