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Background Radiation therapy is a common lifesaving practice in the treatment of cancer, yet there is the potential for error that may cause patient harm or death. Methods Using a retrospective mixed-methods design, we studied a two-year period of event reports submitted by hospitals to the Pennsylvania Patient Safety Reporting System (PA-PSRS) database and targeted those reports that described errors in radiation therapy. We analyzed the relation between the following primary variables: event type, whether it reached the patient, phase of radiation therapy when the risk factor originated, and risk factor (i.e., event impetus). Results Our sample included 245 event reports from 40 hospitals. Among the 245 reports, 60% of the errors reached the patient, 71% of the sample were a wrong dose, and 29% described a delay in treatment. Across all six phases of radiation therapy, 38% of events originated from the treatment planning phase and 40% were from the treatment delivery phase. We identified 23 unique categories of risk factors that acted as the impetus. The most frequently identified were malfunction of hardware/software, wrong contour, absent or wrong accessory, wrong position, and wrong or low-quality images. Conclusions The present study expanded upon many of the prior radiation therapy studies by exploring the relation among the various combinations of the primary variables. The study highlights the current risks in the practice of radiation therapy and the broad range of conditions in which errors may occur. Online Supplement Appendix S1 (https://doi.org/10.33940/001c.155351) provides a list of mitigation strategies aimed at detecting and preventing the risk factors identified in the present study. Plain Language Summary Radiation therapy (RT), in which radiation is administered to the body externally (e.g., beam radiation) or internally (by temporary insertion or permanent implant), is a well-known treatment for cancer. However, RT is complex and nuanced, requiring planning, administration, and monitoring by a large, multidisciplinary care team—and thus comes with its own safety risks for patients and staff. This study of 245 events reported by 40 hospitals from January 1, 2022, to December 31, 2023, identified 23 risk factors across six phases of RT ( before simulation, simulation, treatment planning, pretreatment QA review, treatment delivery , and after treatment completion ). In each event, one of the 23 RT risk factors contributed to a wrong dose error (71%) or delay in treatment (29%). More than half of the wrong dose events (51%) originated from the treatment planning phase and a majority of the delay in treatment events (67%) were associated with treatment delivery . One standout finding is that lengthy treatment delays were frequently attributed to scheduling or ordering errors in the before simulation phase, suggesting that automated tracking systems could be used to mitigate risk. The authors have provided a list of such mitigation strategies aimed at detecting and preventing the risk factors identified in their study. This online supplement is intended as a resource to guide interventions and reduce patient harm in RT.