The study examined the relationship between perfectionism (categorized by adaptive, maladaptive, and non-perfectionist clusters), substance use (i.e., drinking and smoking), and mental health in a large sample of college student (N = 841; M = 19.6 years of age) in a time-lagged design. Students were classified using a two-step cluster analysis where subscales are used in hierarchical and k-means cluster analysis. Results revealed that adaptive perfectionists reported better mental health compared to non-perfectionists and maladaptive perfectionists. Additionally, adaptive perfectionists reported lower levels of alcohol use compared to non-perfectionists. Differences between mental health and alcohol use by cluster were found over time, but not for smoking behaviors. Across all participants, substance use did not mediate the relationship between perfectionism and mental health. Future research directions as well as practical implications are discussed.