This paper has two aims: (1) to replicate the four-dimensional structure of the Drinking Motive Questionnaire Revised (DMQ-R) in a national representative sample from Switzerland, and (2) to validate the relevance of distinguishing drinking motives by inspecting the relations with expected consequences, alcohol use, and alcohol-related and other problems. Confirmatory factor analysis and linear structural equation models were estimated based on answers of 5,617 8th to 10th graders (mean 15.1 years; SD = 0.95). The results confirm the four-dimensional factor structure in general and among subpopulations defined by gender, age, and linguistic region. It could also be confirmed that enhancement motives followed by coping motives were strongly related to alcohol use and heavy drinking, whereas conformity motives were negatively related. Coping motives were related to problems independent of whether they were assessed as alcohol-related or not, while enhancement motives were associated solely with alcohol-related problems. In sum, the results demonstrate the robustness of the DMQ-R and its usefulness for assessing drinking motives among European adolescents from different cultural backgrounds.