To examine associations between past-year mental illness (MI) diagnoses and e-cigarette use status. Data were obtained from the National College Health Assessment, a nationally recognized cross-sectional survey of university students. Participants were recruited from 2-year and 4-year public and private universities across the United States from 2017-2019. The analytic sample included 277291 university students. Self-reported past-year MI diagnosis, binarily coded, served as the primary predictor. The outcome was e-cigarette use status (never, noncurrent, and current user). Multinomial logistic regression models were used to estimate relative risk ratios (RRR) of e-cigarette use, as predicted by past-year MI diagnoses, age, race/ethnicity, sex and gender, sexual identity, geographic region, and other combustible tobacco, alcohol, and marijuana use. Compared to those who had never received any MI diagnosis in the past year, those who did had a 16% higher relative risk (RRR = 1.16, 95% CI: 1.11, 1.20) of being a noncurrent e-cigarette user and a 33% higher relative risk (RRR = 1.33, 95% CI: 1.28, 1.38) of being a current e-cigarette user. Schizophrenia, substance use or addiction, bipolar disorder, and attention deficit and hyperactivity disorder (ADHD) diagnoses demonstrated the strongest associations with noncurrent and current e-cigarette use. Results suggest the need to screen young adults for e-cigarette use and mental health indicators to facilitate early detection and timely intervention for at-risk university students.