BACKGROUND: Despite accumulating evidence indicating that collecting patient-reported outcomes (PROs) and transferring results to the treating health professional in real time has the potential to improve patient well-being and cancer outcomes, this practice is not widespread. OBJECTIVE: The aim of this study was to test the feasibility and acceptability of PROMPT-Care (Patient Reported Outcome Measures for Personalized Treatment and Care), a newly developed electronic health (eHealth) system that facilitates PRO data capture from cancer patients, data linkage and retrieval to support clinical decisions and patient self-management, and data retrieval to support ongoing evaluation and innovative research. METHODS: We developed an eHealth system in consultation with content-specific expert advisory groups and tested it with patients receiving treatment or follow-up care in two hospitals in New South Wales, Australia, over a 3-month period. Participants were recruited in clinic and completed self-report Web-based assessments either just before their upcoming clinical consultation or every 4 weeks if in follow-up care. A mixed methods approach was used to evaluate feasibility and acceptability of PROMPT-Care; data collected throughout the study informed the accuracy and completeness of data transfer procedures, and extent of missing data was determined from participants' assessments. Patients participated in cognitive interviews while completing their first assessment and completed evaluation surveys and interviews at study-end to assess system acceptability and usefulness of patient self-management resources, and oncology staff were interviewed at study-end to determine the acceptability and perceived usefulness of real-time PRO reporting. RESULTS: A total of 42 patients consented to the study; 7 patients were withdrawn before starting the intervention primarily because of changes in eligibility. Overall, 35 patients (13 on treatment and 22 in follow-up) completed 67 assessments during the study period. Mean completeness of patient-reported data was 93%, with 100% accuracy of data transfer. Ten patients completed cognitive interviews, 28 completed evaluation surveys, and 14 completed evaluation interviews at study-end. PROMPT-Care patient acceptability was high-100% (28/28) reported the time to complete the Web-based assessments (average 15 min) as about right, most willing to answer more questions (79%, 22/28 yes), 96% (27/28) found the Web-based assessment easier or same as completing a paper copy, and they valued the self-management resources . Oncology staff (n=5) also reported high acceptability and potential feasibility of the system. CONCLUSIONS: Patients and oncology staff found the PROMPT-Care system to be highly acceptable, and the results suggest that it would be feasible to implement it into an oncology setting. Suggested modifications to the patient assessment survey, clinician access to the reports, and system requirements will be made as part of the next stage of large-scale testing and future implementation of the system as part of routine care. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN1261500135294; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=369299&isReview=true (Archived by WebCite at http://www.webcitation.org/6lzylG5A0).