Substance use disorders (SUDs) in nursing have individual well-being, patient safety, and licensure/regulatory implications. Literature is scarce related to predicting SUDs in registered nurses; this study included specific items surrounding nurses’ psychological trauma. An online survey, consisting of validated scales and investigator-generated items was distributed to 4,000 registered nurses in Indiana with a yield of 1,478 surveys. The World Health Organization: Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) was used as the dependent variable to assess risk of SUDs. Three multivariate regression models with predictive variables for risk of tobacco ( R2 = 0.08), alcohol ( R2 = 0.09), and other substances ( R2 = 0.10) use were found. Of concern, nurses are at moderate risk for tobacco use at 11.6%; alcohol use at 11.6% and for other substances at 10.4%. Each regression model contained distinct predictor variables; however, variables occurring in all three models were: depression, anxiety, and items surrounding psychological trauma (adverse childhood experiences, life events, lateral workplace violence).