OBJECTIVES: Waterpipe smoking is an understudied form of tobacco use with growing popularity among college students and a misconception of relative safety. Our objectives were to identify predictors of persistent waterpipe smoking among college students who have tried using a waterpipe to smoke tobacco in the past. The participants of our study included a sample of University of Houston (UH) students who previously used a waterpipe to smoke tobacco (N=1,141). METHODS: Cross-sectional study through a voluntary online survey in February 2011. Survey questions included demographics (gender, age, race/ethnicity), tobacco use, risk perception, social acceptability, and popularity of waterpipe smoking. Two outcome variables were identified in this study: outcome 1: monthly waterpipe smoking or more versus less than monthly use, outcome 2: weekly waterpipe smoking or more versus less frequent use. Descriptive statistics and chi-square analyses were used to determine the frequencies and associations of participant characteristics and multivariate logistic regression models were carried out to determine predictors of persistent waterpipe use. RESULTS: Among those who previously used a waterpipe, approximately one fifth reported smoking a waterpipe on a monthly basis or more, and 5% reported smoking on a weekly basis or more. Significant predictors of persistent waterpipe use included: White Middle-Eastern ethnicity, Indian Asian or Pakistani Asian ethnicity, past 30-day cigar use, ownership of a waterpipe, believing waterpipe smoking was cool, and longer than 30 minutes waterpipe smoking sessions. Those who believed that waterpipe smoking was harmful to one’s health and those who thought government should evaluate the safety before selling the waterpipes were less likely to become persistent users.  CONCLUSIONS: Findings of this study highlight the importance of developing interventions that address the predictors identified. Educational programs that explain the potential harms of waterpipe smoking and modify the cool image associated may be effective in preventing the spread of this rapidly emerging health hazard.