BACKGROUND: Catastrophic errors in healthcare are rare, yet the consequences are so serious that where possible, special procedures are put in place to prevent them. As systems become safer, it becomes progressively more difficult to detect the remaining vulnerabilities. Using inadvertent intrathecal administration of vinca alkaloids as an example, we investigated whether analysis of incident report data describing low-harm events could bridge this gap. METHODS: We studied nine million patient safety incidents reported from England and Wales between November 2003 and May 2013. We searched for reports relating to administration of vinca alkaloids in patients also receiving intrathecal medication, and classified the failures identified against steps in the relevant national protocol. RESULTS: Of 38 reports that met our inclusion criteria, none resulted in actual harm. The stage of the medication process most commonly involved was 'supply, transport and storage' (15 cases). Seven cases related to dispensing, six to documentation, and four each to prescribing and administration. Defences most commonly breached related to separation of intravenous vinca alkaloids and intrathecal medication in timing (n=16) and location (n=8); potential for confusion due to inadequate separation of these drugs therefore remains. Problems involved in six cases did not align with the procedural defences in place, some of which represented major hazards. CONCLUSIONS: We identified areas of concern even within the context of a highly controlled standardised national process. If incident reporting systems include and encourage reports of no-harm incidents in addition to actual patient harm, they can facilitate monitoring the resilience of healthcare processes. Patient safety incidents that produce the most serious harm are often rare, and it is difficult to know whether patients are adequately protected. Our approach provides a potential solution.