OBJECTIVES: Valid data on factors that increase a health care worker's likelihood of substance use are integral in ensuring professional standards and quality health care for consumers. This study explored the association between nursing specialty and past-year substance use. METHODS: In an anonymous mailed survey, a balanced stratified sample of registered nurses (n = 4438) reported their use of marijuana, cocaine, and prescription-type drugs, as well as cigarette smoking and binge drinking. RESULTS: Prevalence of use of all substances was 32%. Rates varied by specialty, even when sociodemographics were controlled. Compared with nurses in women's health, pediatrics, and general practice, emergency nurses were 3.5 times as likely to use marijuana or cocaine (odds ratio [OR] = 3.5; 95% confidence interval [CI] = 1.5, 8.2); oncology and administration nurses were twice as likely to engage in binge drinking; and psychiatric nurses were most likely to smoke (OR = 2.4; 95% CI = 1.6, 3.8). No specialty differences appeared for prescription-type drug use. CONCLUSIONS: Certain nursing specialties were more likely than others to be associated with substance use. The differences were not explained by demographic characteristics. Inasmuch as a comparison of these results for nurses with prior work on physicians found considerable agreement by specialty, preventive initiatives should consider inter-disciplinary approaches to substance use education.