Amputations confer significant long-term issues, with pain, physical and psychological disability. We present the first two cases of quadruple amputees that have undergone acute Targeted Muscle Reinnervation (TMR) in a specialised centre with multidisciplinary team involvement. Our aims were to reduce pain post-operatively and improve myoelectric control of prostheses. Mr JD and Ms LC, a 55 year old male and a 69 year old female respectively, underwent quadruple amputations with immediate TMR after developing four-limb necrosis from sepsis and disseminated intravascular coagulation. Each patient completed self-reporting questionnaires for each limb at 6, 9 and 12 months post amputation which evaluated wear and use of prostheses, sleep habits, phantom pain, neuroma pain and overall quality of life. Both patients had no neuropathic pain by 6 months post-operatively and considerable reduction or complete resolution in phantom limb pain by 12 months. This coincided with little to no analgesia use by 6 months in both cases and supports the current literature for amputees post TMR. We obtained better myolectric control with Ms LC as she had a two site myoelectric prosthesis and intuitive control with virtual prostheses for bilateral upper limbs. Unfortunately due to funding, the definitive prescription of multi-articulating pattern recognition prosthesis is currently being determined for both patients. Despite this, both have had similar functional outcomes at 12 months with the ability to walk unaided at home or outside on uneven ground. We hope to expand our service in future.