OBJECTIVE There is limited research on adolescents' use of e-cigarettes and other substances. METHODS 2241 Connecticut high school students completed anonymous, cross-sectional surveys assessing e-cigarette and other substance use. We used latent class analysis (LCA) to: (1) classify students based on their past-month use of e-cigarettes, cigarettes, cigars, smokeless tobacco, hookah, blunts, marijuana, and alcohol, and (2) determine if age, sex, or race predicted class membership. RESULTS Past-month e-cigarette use was 11.6%, and use rates for the remaining substances ranged from 2.8% (smokeless tobacco) to 20.7% (alcohol). The optimal latent class solution comprised four classes: (1) primarily abstainers (81.6%; abstainers), (2) primarily e-cigarette and alcohol users (4.6%; E-cigarette-Alcohol), (3) primarily marijuana and alcohol users (6.9%; Marijuana-Alcohol), and (4) primarily users of all products (6.9%; All Products). Compared to abstainers, (1) all substance-using classes comprised older students, (2) the All Products and E-cigarette-Alcohol classes were more likely to comprise males and less likely to comprise Blacks, and (3) the Marijuana-Alcohol class was more likely to comprise Blacks and Latinos. Relative to the All Products and E-cigarette-Alcohol classes, the Marijuana-Alcohol class was more likely to comprise females, Blacks, and Latinos. CONCLUSIONS LCA identified four substance use classes, two of which included elevated e-cigarette use. Class membership differed by age, sex, and race. Additional research should evaluate characteristics that may explain the different product use profiles identified in the current study including cultural differences, peer group norms, and differing perceptions of the harmfulness of each substance.