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 analysing 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 the therapies often have narrow therapeutic windows. Thus, many of the processes are, in NAT terms, interactively complex and tightly coupled within and across systems and are therefore prone to unexpected behaviours that can result in substantial patient harm. To improve safety at the University of North Carolina, Chera et al. have applied the concepts of NAT to their practice to better understand their systems’ behaviour and adopted strategies to reduce complexity and coupling. Furthermore, recognising that you cannot eliminate all risks, they have stressed safety mindfulness among their 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.