This study aimed to determine the prevalence and factors associated with hookah smoking and perceptions of harm among U.S. adults. Data were pooled from the Tobacco Products and Risk Perceptions Surveys conducted separately in the summers of 2014 and 2015, among a probability sample selected from an online research panel. Descriptive, logistic regression, and multinomial logistic regression analyses were conducted. In 2014/2015, prevalence of ever and past 30-day hookah smoking among U.S. adults were 15.8% (95% C.I.: 15.0%, 16.7%) and 1.5% (95% C.I.: 1.2%, 1.8%), respectively. Adults who used other alternative tobacco products had a higher odds of hookah smoking than those who did not. Adults with some college education (AOR, 1.53) and with a college degree or more (AOR, 2.21), those identified as non-Hispanic other (AOR, 1.38) were more likely to be ever hookah smokers. Being a young adult (AOR, 2.7), college-educated (AOR, 2.3), never smoker (AOR, 2.1), and an ever hookah smoker (AOR, 2.8) were associated with lower perceptions of harm. Findings suggest that young college students are at higher risk of smoking hookah and that hookah smoking is more prevalent among individuals who use other tobacco products, such as little cigars and cigarillos, traditional cigars, and e-cigarettes, indicating a distinct group of users of alternative tobacco products. Regarding potential harm of hookah, the study highlights a knowledge gap and misperception especially among young, college-educated, and never smokers. Public health interventions should target these subpopulations to provide them with accurate information on hookah smoking.