PURPOSE: To test whether differences in alcohol use between boys and girls and between northern and southern/central Europe are mediated by social, enhancement, coping, and conformity motives. METHODS: Cross-sectional school-based surveys were conducted among 33,813 alcohol-using 11- to 19-year-olds from northern Europe (Denmark, Estonia, Finland, Ireland, Poland, Scotland, and Wales) and southern/central Europe (Belgium, Hungary, Italy, Portugal, Slovakia, and Switzerland). RESULTS: Particularly in late adolescence and early adulthood, boys drank more frequently and were more often drunk than girls. Instead of mediation, gender-specific motive paths were found; 14- to 16-year-old girls drank more because of higher levels of coping motives and lower levels of conformity motives, whereas 14- to 19-year-old boys drank more because of higher levels of social and enhancement motives. Geographical analyses confirmed that adolescents from southern/central European countries drank more frequently, but those from northern Europe reported being drunk more often. The strong indirect effects demonstrate that some of the cultural differences in drinking are because of higher levels of social, enhancement, and coping motives in northern than in southern/central Europe. CONCLUSIONS: The results from the largest drinking motive study conducted to date suggest that gender-specific prevention should take differences in the motivational pathways toward (heavy) drinking into account, that is, positive reinforcement seems to be more important for boys and negative reinforcement for girls. Preventive action targeting social and enhancement motives and taking drinking circumstances into account could contribute to tackling underage drinking in northern Europe.