Using cluster analysis, 717 students who reported that they had never smoked and the nondrinking 292 students who reported that they had never drank alcohol were classified into four profile groups based on their Pros and Cons of not using and temptation to use. Profiles were labeled Most Protected, Least Positive, Most Negative, and Most Tempted. Profile groups differed significantly on peer pressure, family communication, and use of 11 Transtheoretical Model (TTM) processes of prevention, and applied experiential and behavioral strategies to prevent the onset of smoking and alcohol use. The largest and most consistent differences were on the processes with the Most Protected using more than the Least Positive and Most Tempted groups. Being more actively engaged with the processes of prevention helps to explain why the Most Protected group has had the least amount of substance use over time while the Most Tempted and Least Positive groups had the highest rates of substance use. The consistency and size of differences on the processes support the hypothesis that Most Protected youth may be those who proactively protect themselves from substance use initiation.