Concerns for patient safety persist in clinical oncology. Within several nonmedical areas (eg, aviation, nuclear power), concepts from Normal Accident Theory (NAT), a framework for analyzing failure potential within and between systems, have been successfully applied to better understand system performance and improve system safety. Clinical oncology practice is interprofessional and interdisciplinary, and our therapies often have narrow therapeutic windows. Thus, many of our processes are, in NAT terms, interactively complex and tightly coupled within and across systems and are therefore prone to unexpected behaviors that can result in substantial patient harm. To improve safety at the University of North Carolina, we have applied the concepts of NAT to our practice to better understand our systems' behavior and adopted strategies to reduce complexity and coupling. Furthermore, recognizing that we cannot eliminate all risks, we have stressed safety mindfulness among our staff to further promote safety. Many specific examples are provided herein. The lessons from NAT are translatable to clinical oncology and may help to promote safety.