Currently used prosthetic solutions in upper extremity amputation have limited functionality, owing to low information transfer rates of neuromuscular interfacing. Although surgical innovations have expanded the functional potential of the residual limb, available interfaces are inefficacious in translating this potential into improved prosthetic control. There is currently no implantable solution for functional interfacing in extremity amputation which offers long-term stability, high information transfer rates, and is applicable for all levels of limb loss. In this study, we presented a novel neuromuscular implant, the the Myoelectric Implantable Recording Array (MIRA). To our knowledge, it is the first fully implantable system for prosthetic interfacing with a large channel count, comprising 32 intramuscular electrodes. The purpose of this study was to evaluate the MIRA in terms of biocompatibility, functionality, and feasibility of implantation to lay the foundations for clinical application. This was achieved through small- and large-animal studies as well as test surgeries in a human cadaver. We evaluated the biocompatibility of the system's intramuscular electromyography (EMG) leads in a rabbit model. Ten leads as well as 10 pieces of a biologically inert control material were implanted into the paravertebral muscles of four animals. After a 3-month implantation, tissue samples were taken and histopathological assessment performed. The probes were scored according to a protocol for the assessment of the foreign body response, with primary endpoints being inflammation score, tissue response score, and capsule thickness in µm. In a second study, chronic functionality of the full system was evaluated in large animals. The MIRA was implanted into the shoulder region of six dogs and three sheep, with intramuscular leads distributed across agonist and antagonist muscles of shoulder flexion. During the observation period, regular EMG measurements were performed. The implants were removed after 5 to 6 months except for one animal, which retained the implant for prolonged observation. Primary endpoints of the large-animal study were mechanical stability, telemetric capability, and EMG signal quality. A final study involved the development of test surgeries in a fresh human cadaver, with the goal to determine feasibility to implant relevant target muscles for prosthetic control at all levels of major upper limb amputation. Evaluation of the foreign body reaction revealed favorable biocompatibility and a low-grade tissue response in the rabbit study. No differences regarding inflammation score (EMG 4.60 ± 0.97 [95% CI 4.00 to 5.20] versus control 4.20 ± 1.48 [95% CI 3.29 to 5.11]; p = 0.51), tissue response score (EMG 4.00 ± 0.82 [95% CI 3.49 to 4.51] versus control 4.00 ± 0.94 [95% CI 3.42 to 4.58]; p > 0.99), or thickness of capsule (EMG 19.00 ± 8.76 µm [95% CI 13.57 to 24.43] versus control 29.00 ± 23.31 µm [95% CI 14.55 to 43.45]; p = 0.29) were found compared with the inert control article (high-density polyethylene) after 3 months of intramuscular implantation. Throughout long-term implantation of the MIRA in large animals, telemetric communication remained unrestricted in all specimens. Further, the implants retained the ability to record and transmit intramuscular EMG data in all animals except for two sheep where the implants became dislocated shortly after implantation. Electrode impedances remained stable and below 5 kΩ. Regarding EMG signal quality, there was little crosstalk between muscles and overall average signal-to-noise ratio was 22.2 ± 6.2 dB. During the test surgeries, we found that it was possible to implant the MIRA at all major amputation levels of the upper limb in a human cadaver (the transradial, transhumeral, and glenohumeral levels). For each level, it was possible to place the central unit in a biomechanically stable environment to provide unhindered telemetry, while reaching the relevant target muscles for prosthetic control. At only the glenohumeral level, it was not possible to reach the teres major and latissimus dorsi muscles, which would require longer lead lengths. As assessed in a combination of animal model and cadaver research, the MIRA shows promise for clinical research in patients with limb amputation, where it may be employed for all levels of major upper limb amputation to provide long-term stable intramuscular EMG transmission. In our study, the MIRA provided high-bandwidth prosthetic interfacing through intramuscular electrode sites. Its high number of individual EMG channels may be combined with signal decoding algorithms for accessing spinal motor neuron activity after targeted muscle reinnervation, thus providing numerous degrees of freedom. Together with recent innovations in amputation surgery, the MIRA might enable improved control approaches for upper limb amputees, particularly for patients with above-elbow amputation where the mismatch between available control signals and necessary degrees of freedom for prosthetic control is highest.