Background: Hookah use has been spreading rapidly. In 2015, we explored hookah use patterns and their association with substance use among students in the City University of New York, the largest, most diverse public university system in the United States. Methods: A representative sample of students aged 18-30 were surveyed on their tobacco/nicotine product use behaviors, including hookah, cigarettes, cigars, pipes, cigarillos and e-cigarettes. Multivariate logistic regression models were conducted to compare differences in sociodemographic characteristics and other substance use behaviors among two groups: exclusive hookah users and poly-tobacco-hookah (hookah + other products) users. Results: Among 2,986 respondents, 61% were female and mean age was 22.5 years. Current hookah use was 13%. Among those, 68% were exclusive hookah users, and 32% were poly- tobacco-hookah users. There were no differences between groups on most sociodemographic (i.e. gender, marital status, employment, income) or use characteristics (e.g., ownership of hookah). Compared to exclusive hookah users, poly-tobacco-hookah users were more likely to be 26-28 years compared to 23-25 as reference (Adjusted odds ratio (AOR) =3.1, p<0.05) and less likely to be Caribbean/West Indian (AOR= 0.28, p <0.01). Poly-tobacco-hookah users were more likely to report past year binge drinking (i.e., more than 6 drinks on one occasion) (AOR=4.2, p<0.001) and past year marijuana use (AOR=3.2, p<0.001) compared to exclusive hookah users. Conclusion: Hookah use was relatively common among our sample and poly-tobacco-hookah users were less likely than exclusive users to be Caribbean/West Indian. There were more exclusive hookah than poly-tobacco-hookah users. The latter group was significantly more at risk of binge drinking and marijuana use. This suggests that poly-hookah-use may be more prevalent among those at higher risk for substance use. Future research should evaluate different patterns of hookah use behaviors to inform the design of responsive interventions for lower and higher risk hookah users.