Background and purpose: Industrial companies use failure mode and effect analysis (FMEA) to improve quality. Our objective was to describe an FMEA and subsequent interventions for an automated intraoperative electron radiotherapy (IOERT) procedure with computed tomography simulation, pre-planning, and a fixed conventional linear accelerator. Material and methods: A process map, an FMEA, and a fault tree analysis are reported. The equipment considered was the radiance treatment planning system (TPS), the Elekta Precise linac, and TN-502RDM-H metal–oxide-semiconductor-field-effect transistor in vivo dosimeters. Computerized order-entry and treatment-automation were also analyzed. Results: Fifty-seven potential modes and effects were identified and classified into ‘treatment cancellation’ and ‘delivering an unintended dose’. They were graded from ‘inconvenience’ or ‘suboptimal treatment’ to ‘total cancellation’ or ‘potentially wrong’ or ‘very wrong administered dose’, although these latter effects were never experienced. Risk priority numbers (RPNs) ranged from 3 to 324 and totaled 4804. After interventions such as double checking, interlocking, automation, and structural changes the final total RPN was reduced to 1320. Conclusions: FMEA is crucial for prioritizing risk-reduction interventions. In a semi-surgical procedure like IOERT double checking has the potential to reduce risk and improve quality. Interlocks and automation should also be implemented to increase the safety of the procedure.