The-Optimal-Lymph-Flow health IT system (TOLF) is a patient-centered, web-and-mobile-based educational and behavioral health IT system focusing on safe, innovative, and pragmatic self-care strategies for lymphedema symptom management. The purpose of this study was to evaluate usability, feasibility, and acceptability of TOLF among the end-user of breast cancer survivors. Two types of usability testing were completed with 30 breast cancer survivors: heuristic evaluation and end-user testing. Each participant was asked to think aloud while completing a set of specified tasks designed to explicate and freely explore the system features. A heuristic evaluation checklist, the Perceived Ease of Use and Usefulness Questionnaire, and The Post Study System Usability Questionnaire were used to evaluate usability of the system. Open-ended questions were used to gather qualitative data. Quantitative data were analyzed using descriptive statistics and qualitative data were summarized thematically. Breast cancer survivors were very satisfied with the system: 90% (n=27) rated the system having no usability problems; 10% (n=3) noted minor cosmetic problems: spelling errors or text font size. The majority of participants 96.6% (n=29) strongly agreed that the system was easy to use and effective in helping to learn about lymphedema, symptoms and self-care strategies. Themes from the qualitative data included empowerment, high quality information, loving avatar simulation videos, easy accessibility, and user-friendliness. This usability study provided evidence on breast cancer survivor's acceptance and highly positive evaluation of TOLF's usability as well as feasibility of using technologically-driven delivery model to enhance self-care strategies for lymphedema symptom management. •Many breast cancer survivors suffer from daily distressing symptoms related to lymphedema, requires ongoing symptom management.•Health information technology (IT) plays a significant role in improving self-care, patient-clinician communication, and access to health information by patients.•The-Optimal-Lymph-Flow health IT system (TOLF) is a patient-centered, web-and-mobile-based educational and behavioral health IT system focusing on safe, innovative, and pragmatic self-care strategies for lymphedema symptom managemet.•This usability study provided evidence that supports the usefulness of TOLF in terms of breast cancer survivor’s acceptance, user-friendliness, and feasibility of using technologically-driven delivery model to enhance self-care strategies for lymphedema symptom management.