ABSTRACT Stigma is a public health concern. Stigmatizing attitudes toward persons with substance use disorders (SUDs) can adversely impact clinical care and outcomes. Beliefs about SUD, prior experience and familiarity to persons with SUD, and educational curricula drive attitudes among health-care workers. In 2019, nursing and nursing assistant students were recruited through an online survey platform. Participants completed an SUD knowledge test and a survey assessing education, beliefs, personal experience, and confidence in recognizing the signs and symptoms of SUD. One hundred and ten health-care students (nursing students, n = 67 and nursing assistant students, n = 43) completed the survey. Among nursing assistant students, endorsing a disease model of addiction (F(2, 40) = 5.83, p < .001, R 2 = .23), and personal familiarity with SUD (F(2, 40) = 4.46, p < .001, R 2 = .18), were significantly positively predictive of positive regard toward working with persons with SUD. For nursing students, endorsing a disease model of addiction, educational curricula involving persons with SUD, and personal familiarity were significantly positively predictive of positive regard toward working with persons with SUDs (F(2, 61) = 11.52, p < .001, R2 = .36). Interventions to mitigate drug-related stigma among health-care students should center students with personal familiarity, promote the disease concept of addiction, and incorporate contact-based training.