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Abstract: Phantom limb pain (PLP) represents a significant challenge after amputation. This study investigated the use of phantom motor execution (PME) and phantom motor imagery (PMI) facilitated by extended reality (XR) for the treatment of PLP. Both treatments used XR, but PME involved overt execution of phantom movements, relying on the decoding of motor intent using machine learning to enable real-time control in XR. In contrast, PMI involved mental rehearsal of phantom movements guided by XR. The study hypothesized that PME would be superior to PMI. A multicenter, double-blind, randomized controlled trial was conducted in 9 outpatient clinics across 7 countries. Eighty-one participants with PLP were randomly assigned to PME or PMI training. The primary outcome was the change in PLP, measured by the Pain Rating Index, from baseline to treatment cessation. Secondary outcomes included various aspects related to PLP, such as the rate of clinically meaningful reduction in pain (CMRP; >50% pain decrease). No evidence was found for superiority of overt execution (PME) over imagery (PMI) using XR. PLP decreased by 64.5% and 68.2% in PME and PMI groups, respectively. Thirty-seven PME participants (71%) and 19 PMI participants (68%) experienced CMRP. Positive changes were recorded in all other outcomes, without group differences. Pain reduction for PME was larger than previously reported. Despite our initial hypothesis not being confirmed, PME and PMI, aided by XR, are likely to offer meaningful PLP relief to most patients. These findings merit consideration of these therapies as viable treatment options and alternatives to pharmacological treatments., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)