Associations between the emerging trend of waterpipe tobacco smoking and mental health among college students have not been sufficiently explored. This study analyzed data collected from 152 academic institutions that participated in the National College Health Assessment during the 2008-2009 academic year to examine associations between mental health and waterpipe tobacco smoking among college students (N = 100,891). For comparison, cigarette smoking was also examined. Associations with mental health variables were very strong for cigarette smoking but only moderate for waterpipe smoking. Study implications and limitations are noted.