Certified registered nurse anesthetists (CRNAs) are exposed daily to highly addictive substances and stressful work environments, placing them at risk for substance use disorders (SUDs). Previous research, which is scarce, indicated that drugs of choice were opioids and propofol. Therefore, the purpose of this study was to investigate predictors of SUD risk using the World Health Organization Alcohol, Smoking and Substance Involvement Screening Test. From June to July 2020, an online survey was sent via the American Association of Nurse Anesthesiology Research Survey Service to 3,000 CRNAs with a response of approximately 225 members. CRNAs were found to be at a moderate risk for SUDs in the following categories: 10.27% for tobacco, 23.56% for alcohol, and 6.28% for cannabis. Regression analysis by substance category includes robust, differing models in this homogeneous sample. Predictors for all three models include a collection of demographic variables, religiosity, anxiety, difficulties due to anxiety, depression, substance use history, contact with the American Association of Nurse Anesthesiology Peer Assistance Program, and organizational support. Over 10% of CRNAs are at risk for developing tobacco use disorder, and almost one quarter of those surveyed are at a moderate risk for developing alcohol use disorder. These data are of concern and may indicate a shift of preferred substances used by CRNAs from controlled substances to alcohol.