BACKGROUND: The Smart Angel home medical device allows ambulatory surgery patients to monitor their own health by taking their blood pressure and oxygen levels and answering a health questionnaire from home. Currently, this device is a prototype in the design phase, and no usability evaluation has been performed. This preventive device must be usable by patients with different profiles; however, it is important to select patients carefully to ensure their safety when using the device. As such, it would be interesting to know how to select or exclude patients. However, the links between user characteristics and the usability of this home medical device remain unclear. OBJECTIVE: This study aims to better understand the links between certain characteristics of potential patients (ie, age, education, technophilia, and health literacy) and the usability (ie, effectiveness, efficiency, and satisfaction) of Smart Angel, as defined by the ISO 9241-11. METHODS: We conducted an experimental study involving 36 participants investigating the effects of 4 patient characteristics (ie, age, education, technophilia, and health literacy) on usability, measured in terms of effectiveness, efficiency, and satisfaction. A mixed methods approach (subjective vs objective) using a variety of standard instruments was adopted (direct observation, video analysis, and questionnaires). First, to help participants project themselves into the real use of the Smart Angel device, they watched a scenario in a video. Second, the participants completed a set of questionnaires to show the extent of their health literacy level (Newest Vital Sign [NVS] and the Health Literacy Survey [HLS]) and then operated Smart Angel devices. Efficiency (ie, handling time) and effectiveness (ie, number of handling errors) measures were collected by video analysis. Satisfaction measures were collected by a questionnaire (System Usability Scale [SUS]). The qualitative observational data were coded using inductive analysis by 2 independent researchers specialized in cognitive psychology and cognitive ergonomics. RESULTS: The results show a moderate and positive correlation between age and effectiveness (r=0.359; P=.03) and efficiency (r=0.357; P=.03). There is strong correlation between health literacy scored by the NVS and effectiveness (r=0.417; P=.01), efficiency (r=-0.38; P=.02), and satisfaction (r=0.45; P=.006). However, there is a weak correlation between technophilia and usability and no relationship between education level and usability. CONCLUSIONS: Our results show that literacy level and age are 2 important factors to consider when selecting future users of the Smart Angel device to ensure patient safety. This study also serves as an example promoting mixed methodologies in assessments of medical device usability that cannot be performed under real-world conditions.