Background: Medication discrepancies consist of unexplained differences between medication lists at different transition points of care; they are a threat to patient safety. These discrepancies can be solved through medication reconciliation (MedRec), a complex and time-consuming process. Several approaches to optimizing MedRec have been encouraged, including the development of information technology (IT) tools and patient engagement. The SEAMPAT project aims to develop a MedRec IT platform based on two applications (one for the patient, the "patient app", the other for healthcare professionals), which were developed using a three-iteration user-centered design. The patient app presents the patient with a medication list compiled from different medication resources. Objective: To evaluate the usability and usefulness of the third iteration of the patient app, from the perspective of different categories of users, with the aims of making recommendations for wider use and informing further research. Methods: We performed a four-month user-centered observational study. After a kick-off session, patients, identified through purposive sampling, were invited to use the patient app at home, to update their medication lists whenever required. Quantitative and qualitative data were collected at different time points to evaluate three dimensions of usability (efficiency, satisfaction, and effectiveness), as well as usefulness. Participants completed two questionnaires on satisfaction and usefulness (including the system usability scale, SUS) at the kick-off and the end of the study. Effectiveness was assessed by measuring the completeness and correctness (i.e. medication discrepancies) of the final medication list generated by the patient application. Qualitative data were collected from observations at different time points and from semi-structured interviews at the end of the study. Results: Forty-eight patients agreed to participate and 42 completed the study, of whom 32 connected at least once to the application at home. Sixty-nine percent of patients considered the patient app to be acceptable (SUS Score ≥ 70) and perceived usefulness was high. The medication list was complete for a quarter of the patients and there was a median of two discrepancies per patient. The main causes were technology-related. The qualitative data enabled the identification of several barriers and, thus, of approaches to optimizing usability and usefulness. These relate to both functional (e.g. access, on-screen display, additional functionalities) and non-functional aspects (e.g. patient awareness, concordance between patient and physician) of the application. For future adoption of the tool, it will be important to address these issues. Conclusions: Our findings highlight the importance and value of user-centered usability testing of a patient application implemented in "real-world" conditions. We believe our study also underlines the need to take patients' points of view into consideration. To achieve adoption and sustained use by...