Background: Nursing is a notoriously high-stress occupation emotionally taxing and physically draining, with a high incidence of burnout. In addition to the damaging effects of stress on nurses' health and well being, stress is also a major contributor to attrition and widespread shortages in the nursing profession. Although there exist promising in-person interventions for addressing the problem of stress among nurses, the experience of our group across multiple projects in hospitals has indicated that the schedules and workloads of nurses can pose problems for implementing in-person interventions, and that web-based interventions might be ideally suited to addressing the high levels of stress among nurses. Purpose: The purpose of this study was to evaluate the effectiveness of the web-based BREATHE: Stress Management for Nurses program. Methods: The randomized controlled trial was conducted with 104 nurses in five hospitals in Virginia and one hospital in New York. The primary outcome measure was perceived nursing-related stress. Secondary measures included symptoms of distress, coping, work limitations, job satisfaction, use of substances to relieve stress, alcohol consumption, and understanding depression and anxiety. Results: Program group participants experienced significantly greater reductions than the control group on the full Nursing Stress Scale, and six of the seven subscales. No other significant results were found. Moderator analysis found that nurses with greater experience benefitted more. Conclusion: Using a web-based program holds tremendous promise for providing nurses with the tools they need to address nursing related stress. (C) 2016 Elsevier Inc. All rights reserved.