Depression impacts 9.4% of the adult population in the United States, and it is known to impact work performance. Nurses with depression are not only likely to suffer themselves, but their illness may have an impact on their coworkers and potentially the quality of care they provide. Thus, the purpose of this study was to determine the prevalence of depression in a random sample of hospital-employed nurses to determine individual and workplace characteristics that are associated with depression. A cross-sectional survey design of 1171 registered nurses was used. Measures included individual characteristics, workplace characteristics, work productivity, and depression (9-item Patient Health Questionnaire). Data analysis demonstrated a depressive symptom rate of 18%. The linear regression model accounted for 60.6% of the variation in the 9-item Patient Health Questionnaire depression scores. Body mass index, job satisfaction, number of health problems, mental well-being, and health-related productivity had significant relationships with depression (P < .05). Hospital-employed nurses have higher rates of depressive symptoms than national norms. Advanced practice nurses can assist with educating nurses on recognizing depression and confidential interventions, including the use of computerized cognitive-based therapy.