The guideline highlights knowledge, competencies and behaviours that recognize, prevent and mitigate fatigue; educational requirements and strategies; policy changes at organizational and system levels needed to support and sustain practices that prevent and mitigate fatigue; implementation strategies and tools; evaluation criteria and tools; and future research opportunities. The purpose of this best practice guideline is to provide evidence-informed recommendations for individuals, systems, and organizations to identify and describe: practices that result in preventing and mitigating fatigue for nurses and other health-care professionals; System resources that support practices to prevent fatigue; organizational cultures, values andresources that support effective practices to prevent fatigue; personal resources that can be used to prevent or mitigate fatigue; and anticipated outcomes when fatigue is effectively managed, thereby fostering healthy work environments. Such environments will support positive outcomes for patients/clients, organizations and systems. This guideline will serve to support health care professionals in their quest to prevent and address fatigue in the workplace as part of creating healthy work environments.