The aim of the current study was to characterize the prevalence of latent groups in terms of smoking, hookah, and alcohol in a sample of Iranian high school students. In this cross-sectional study, 4,422 high school students were assessed in East Azerbaijan Province, Iran. Latent class analysis was applied to determine the subgroups and prevalence of each class using the procLCA in SAS 9.2 software. The prevalence of hookah smoking was the highest among the other substances and had the greatest abuse among males than females. Nearly 86%, 9.5%, and 4.6% of the participants were low risk, tobacco experimenter, and high risk, respectively. The odds ratio indices of membership in each class, compared with the first class, associated with the independent variables. A fair number of students, males in particular, were identified as high risk-takers. Considering the simultaneous incidence of multiple high-risk behaviors, interventions must cover multiple aspects of the issue at the same time.