The Prevention Paradox applies when low-risk individuals in a population contribute the most cases of a condition or problem behavior by virtue of their being in the majority, thereby recommending a universal or whole of population approach to prevention. The application of the Prevention Paradox was examined for the distribution of known social and developmental risk factors of multiple problem behaviors identifiable in Australian teenagers and their association with different patterns of alcohol, tobacco, cannabis, and other illicit drug use. A cross-sectional survey of over 9,000 Victorian high school children, which included a sample of year 11 students (average age 16 years) was analyzed, along with a large cohort study that has followed Victorian children from infancy to 21 years of age at 18 month intervals using mail surveys. Different degrees and intensities of drug use were examined. The results indicated that the measures of social and developmental risk and protection predicted more hazardous drug use in both the cross-sectional and the longitudinal studies. This association was more pronounced for the illicit drugs and also for more intense levels of use of each drug type. The relationship between broad social and developmental risk status of the adolescents and their use of drugs was much closer and more significant in the cross-sectional than in the longitudinal study. This pattern of results strongly supports the view that social and developmental risk factors in late childhood and early adolescence contribute significantly to frequent and heavy drug use and dependence in the late teenage years. Community prevention approaches should combine an emphasis on preventing developmental risk and strengthening protective factors while also strengthening universal regulatory systems and harm reduction. 7 figures, 16 references