BACKGROUND Frequent transitions of care often lead to patient safety events due to inaccurate information sharing or poor communication. Active engagement of patients with cancer and their families in managing and reporting patient safety events is indispensable to achieving safe and effective care transitions and optimal outcomes. A patient-centered reporting system is expected to guide and engage patients with cancer in self-reporting medication safety events from home and increase the understanding of the nature and causes of patient safety events outside health care systems that have been under-reported historically. However, there are challenges in initiating and engaging people with cancer in the use of technology systems for medication safety self-monitoring and reporting from home. OBJECTIVE To assess oncology patients’ perceptions of medication and communication safety during care transitions and their willingness to use digital technologies to self-report medication safety events from home, and identify factors associated with their technology acceptance. METHODS We conducted a cross-sectional survey study with adult patients with breast, prostate, lung, or colorectal cancer (n=204) who had experienced care transitions from hospitals or clinics to home in the past year. Surveys were conducted by phone, online, or mail between December 2021 and August 2022. Participants’ perceptions of medication and communication safety and perceived usefulness, ease of use, attitude toward use, and intention to use a technology system to report their medication safety events from home were assessed as outcomes. Potential personal, clinical, and psychosocial factors were analyzed for their associations with participants’ technology acceptance by bivariate correlation analyses and multiple logistic regression modeling. RESULTS Participants reported strong perceived medication and communication safety which positively correlated with their medication self-management ability and patient activation. Most participants perceived a medication safety self-reporting system was useful (77.5%) and easy to use (77.0%), had a positive attitude toward use (79.4%), and were willing to use such a system (63.2%). Participants who had a part- or full-time job (OR 3.40; 95% CI, 1.26-9.19), prior technology use experience (OR 3.80; 95% CI, 1.73-8.36), a higher level of patient activation (OR 1.83; 95% CI 1.12-2.98), a stronger perception of communication safety (OR 1.64; 95% CI, 1.08-2.47), or a stronger perception of the importance of receiving feedback (OR 3.27; 95% CI, 1.37-7.78) were more likely to use the system. CONCLUSIONS Oncology patients were willing and able to use digital technologies to report their medication safety events from home. Improving patient activation and medication self-management abilities may potentially improve their understanding and prioritization of medication safety events and engage them in using digital technologies for safety event reporting. Developing a patient-centered medication safety event reporting system is expected to address oncology patients’ safety concerns, meet their individual needs, and hold promise to improve the quality of care.