E-cigarette use among young adults is a major public health concern. Approximately 17.7-40% of college students have tried or are currently using e-cigarettes. While a few studies have examined e-cigarette use among youth, opportunity exists to understand psychosocial factors that influence college students' e-cigarette behavior. The main purpose of this study is to examine the associations between the constructs of self-efficacy, knowledge, depression and anxiety symptoms, and e-cigarette use among college students. A retrospective cross-sectional survey (20-items) design was used for data collection. Bivariate analysis and analysis of variance (ANOVA) were used to evaluate associations between the independent variables and the dependent variable. A total of 872 college students between the ages of 18 and 25 completed the survey in Qualtrics. A significant association between gender and frequency of e-cigarette use was found (χ 2 = 22.94, p < .001). ANOVA results showed significant relationships between knowledge [F (3, 808) = 9.01, p < 0.001], self-efficacy [F (3, 808) = 4.85, p < 0.01], depression [F (3,808) = 8.31, p < .05], and e-cigarette use. Post hoc analysis revealed students who never used e-cigarettes scored higher on knowledge and self-efficacy than students who used every day, somedays or rarely, indicating never-users have higher knowledge of negative effects associated with e-cigarette use and have higher self-confidence than e-cigarette users. The study's findings highlight that modifiable factors such as knowledge about harmful effects of e-cigarettes and self-confidence are associated with low e-cigarette use. Interventions could be designed to target these modifiable factors.