Purpose: To identify subgroups of college students with distinct profiles of traditional and alternative types of tobacco, alcohol, and other substance use and to examine how demographic characteristics and academic and social activities are associated with subgroup membership. Methods: We used latent class analysis to characterize subgroups of individuals in their fourth-year of college based on their patterns of seven substance use behaviors: extreme heavy episodic drinking (HED), cigarette use, cigar/cigarillo/little cigar use, smokeless tobacco use, hookah use, marijuana use, and non-medical prescription drug use. Demographic characteristics and academic and social activities were then incorporated as predictors of these latent classes. Results: We identified five classes defined by unique behavior patterns: (1) Non/Low Users, (2) Non-Hookah Tobacco Users, (3) Extreme HED & Marijuana Users, (4) Hookah and Marijuana Users, and (5) Poly-Substance Users. Being male, older, and involved in sports were associated with greater odds of being in the Poly-Substance User class compared to the Low/No User class, and participating in an honors society and reporting more positive peer relationships were associated with being in the Hookah and Marijuana User class compared to the Low/No User class. Conclusion: Our findings of unique characteristics in the subgroups identified suggest that college substance users are a heterogeneous population requiring different targeted interventions. Of particular concern are subgroups with high rates of alternative tobacco products, as perceived risks of use may be inaccurate and this is not currently a focus of college substance use prevention interventions. (C) 2015 Elsevier Ltd. All rights reserved.