Background Radiotherapy practice for cancer treatment is resource-intensive and demands optimised processes for patient throughput while guaranteeing the quality and safety of the therapy. With the COVID-19 pandemic, ad-hoc changes in the operation of radiotherapy centres became necessary to protect patients and staff. This simulation study aimed to quantify the impact of designated COVID-19 protection measures and pandemic-related staff absence on patient waiting times and throughput. The approach also enables analysis of protective measures and process adjustments for future business disruptions. Methods A discrete event simulation model of a stand-alone radiotherapy centre was developed and used to analyse changes in patient flow when implementing COVID-19 protection measures and experiencing staff absence. The simulation results support business continuity planning and decision-making in radiotherapy. In total, twenty-one scenarios in three categories were analysed. Category 1 scenarios investigated the effect of healthcare staff and equipment shortfalls. Category 2 scenarios simulated the impact of additional COVID-19 protection measures at low COVID-19 incidence rates, while category 3 scenarios evaluated the changes at high incidence rates. Results The simulation results suggested increased patient waiting times when staff is absent. Most scenarios of the three categories behave similarly despite increased patient waiting times due to COVID-19 protection measures in categories 2 and 3. The most significant increase in patient waiting times occurs when only two radiation therapists are available. The absence of a linear accelerator for cancer treatment also leads to increased waiting times. Scenarios where one administrator is absent show the longest average and maximum waiting times for low COVID-19 incidence rates. COVID-19 protection measures reduce patient throughput. In all scenarios, with reduced patient throughput, follow-up radiation appointments were affected. Conclusions The simulated scenario results suggest that appropriate staffing of the radiotherapy centre during a pandemic crisis is essential and that staff absence can lead to prolonged patient waiting times and reduced throughput with severe continuity of care consequences. The simulation model demonstrated that centre administrators are a bottleneck if they must perform COVID-19 protection measures in addition to their administrative duties. The effect could be mitigated by outsourcing COVID-19 protection tasks to external service providers or other centre staff.