Substance use and sexual behavior are highly prevalent on college campuses (Arria et al., 2017; American College Health Association, 2018; Schulenberg et al., 2017). Substance misuse and risky sex can lead to adverse consequences (Furman & Collibee, 2014; Patrick & Terry-McElrath, 2016; Read, Haas. Radomski, Wickham, & Borish, 2016). There is high comorbidity between anxiety, substance use, and substance use disorders (Wolitzky et al., 2018). Existential anxiety may be a form of anxiety that is relevant to the college experience because college aged emerging adults are coping with existential issues, e.g., freedom, isolation, meaninglessness, and death, often for the first time. In a sample of undergraduate students, existential concerns predicted higher reports of binge drinking behavior. Existential concerns did not predict cannabis use or unprotected vaginal sex. Moderation analyses indicated that variables such as coping, and mindfulness are variables of interest that require further research to understand their influence on risky behavior as they relate to existential anxiety. Supplemental analyses revealed that a focus on construct validity and continued measurement development for assessing existential concerns is critical. Various existential themes (i.e., isolation, meaning, freedom) were found to be more strongly associated with risky behavior. This study demonstrates the importance of considering the role existential anxiety plays in engagement of high-risk behaviors among college students.