Phantom motor execution (PME) facilitated by augmented/virtual reality (AR/VR) and serious gaming (SG) has been proposed as a treatment for phantom limb pain (PLP). Evidence of the efficacy of this approach was obtained through a clinical trial involving individuals with chronic intractable PLP affecting the upper limb, and further evidence is currently being sought with a multi-sited, international, double blind, randomized, controlled clinical trial in upper and lower limb amputees. All experiments have been conducted in a clinical setting supervised by a therapist. Here, we present a series of case studies (two upper and two lower limb amputees) on the use of PME as a self-treatment. We explore the benefits and the challenges encountered in translation from clinic to home use with a holistic, mixed-methods approach, employing both quantitative and qualitative methods from engineering, medical anthropology, and user interface design. All patients were provided with and trained to use a myoelectric pattern recognition and AR/VR device for PME. Patients took these devices home and used them independently over 12 months. We found that patients were capable of conducting PME as a self-treatment and incorporated the device into their daily life routines. Use patterns and adherence to PME practice were not only driven by the presence of PLP but also influenced by patients’ perceived need and social context. The main barriers to therapy adherence were time and availability of single-use electrodes, both of which could be resolved, or attenuated, by informed design considerations. Our findings suggest that adherence to treatment, and thus related outcomes, could be further improved by considering disparate user types and their utilization patterns. Our study highlights the importance of understanding, from multiple disciplinary angles, the tight coupling and interplay between pain, perceived need, and use of medical devices in patient-initiated therapy.