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Background: Self-monitoring of blood glucose (SMBG) is of paramount relevance for type 2 diabetes mellitus (T2DM) patients. However, past evidence shows that there are physical and cognitive issues that might limit the usage of glucometers by T2DM patients aged 65 years and over. Objective: Our aim was to investigate the physical and cognitive issues related to the usage of glucometers by T2DM patients aged 65 years and over. Materials and Methods: The extant literature was analysed to define an original framework showing the logical nexus between physical and cognitive issues and quality of life. Then we collected evidence addressing the specific case of the Accu-Chek® Instant glucometer produced by Roche Diabetes Care GmbH, which implements new features claiming to improve usability. We conducted 30 interviews with T2DM patients aged 65 years and over, three interviews with senior nurses, and a focus group with three senior physicians and three senior nurses. Results: From the interviews, both patients and nurses declared that they were generally satisfied with the Accu-Chek® Instant glucometer’s characteristics. In the focus group, the results were commented on and, in the light of some diverging answers, improvements have been set up for future implementation. Conclusions: Our study produces evidence and future suggestions about the usage of glucometers by type 2 diabetes patients aged 65 years and over.