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Terminal neuromas resulting from severe nerve injuries and traumatic or surgical limb amputations can become a source of pain, and significantly impair patients' quality of life. Recently, the number of patients with peripheral nerve injuries increased due to modern war conflicts, natural disasters, and traffic accidents. This study investigated the efficacy of the epineural sheath jacket (ESJ) as a novel technique for neuroma prevention in the rat sciatic nerve model.A 20-mm segment of the right sciatic nerve was excised in 18 Lewis rats, and the animals were divided into 3 experimental groups (n = 6/group): group I—control, nerve stump without protection; group II—muscle burying group, nerve stump buried in the muscle; group III—ESJ group, nerve stump protected by ESJ. The ESJ was created from the excised sciatic nerve and applied as a “cap” over the proximal nerve stump. The presence of neuropathic pain was assessed weekly by pinprick test and Tinel sign, up to 24 weeks postsurgery. At 24 weeks, assessments, such as macroscopic evaluation, retrograde neuronal labeling analysis, histomorphometry, and neural/connective tissue ratio were performed.Epineural sheath jacket significantly reduced neuroma formation, which was associated with decreased Tinel sign (16.7%, P < 0.05) response compared with the nerve stump control. Moreover, ESJ reduced axonal sprouting, bulb-shaped nerve ending formation and perineural adhesions, as confirmed by macroscopic evaluation. Histological evaluation confirmed that nerve stumps protected with the ESJ showed less fibrosis and presented well-organized axonal structure. Neural/connective tissue ratio and retrograde neuronal labeling analysis revealed significantly improved results in the ESJ group compared to the control nerve stump group (P = 0.032 and P = 0.042, respectively).The protective effect of the ESJ against neuroma formation was confirmed by behavioral and histological analyses, showing outcomes comparable to the muscle burying technique—the criterion standard of neuroma management.