28 patients (30 limbs) were included in this study comparing Targeted Muscle Re-innervation (TMR) and a standard surgical treatment involving neuroma excision and burial into nearby muscle in patients with major limb amputations above the wrist or ankle. The primary outcomes of interest were the worst residual limb pain and phantom limb pain, measured using a numerical rating scale (NRS). Secondary outcomes of interest included residual limb pain and phantom limb pain as measured by the Patient Reported Outcomes Measurement Information Scale (PROMIS; intensity, behaviour, interference sub-scores), nerve volume, and the Neuro-quality-of-life (QoL) outcome. Follow up was performed 1 year post-treatment and at the patient's final follow up. Results of the study revealed no significant differences in the change in pain from baseline in all pain outcomes, at all time points between the TMR and standard group, with the exception of the change in worst NRS phantom limb pain from baseline at final follow up, which was significantly in favour of the TMR group. Nerve volume was lower in the TMR group compared to the standard group.