This scientific statement from the American Heart Association (AHA) reviews the current state of knowledge on safety issues in the operating room (OR) and provides detailed recommendations for hospitals to implement to improve safety and patient outcomes. These recommendations include using checklists and formal handoff protocols for every procedure, teamwork training and other approaches to enhance safety culture, applying human factors engineering principles to optimize OR design and minimize fatigue, and taking steps to discourage disruptive behavior by clinicians. AHA scientific statements, which are considered the standard of care for cardiac patients, have traditionally focused on clinical issues, but this article (and an earlier statement on medication error prevention) illustrates the critical importance of ensuring safety in this complex group of patients.