ObjectiveTo investigate the effectiveness of incorporating small gap anastomosis (SGA) and epineurial sheath tube (EST) sleeve coaptation into conventional targeted muscle reinnervation (TMR) for the treatment of post-amputation painful stump neuroma (PSN), and to compare the outcomes between different types of nerves undergoing coaptation, namely sensory nerves and mixed nerves. MethodsThe clinical data of 30 patients with PSN who underwent TMR combined with SGA and EST sleeve coaptation between January 2020 and January 2025 were retrospectively analyzed. According to the type of nerve undergoing coaptation, the patients were divided into a sensory nerve coaptation group (group A, 13 cases) and a mixed nerve coaptation group (group B, 17 cases). There was no significant difference between the two groups in age, gender, amputation site, cause of amputation, or preoperative visual analogue scale (VAS) pain score (P>0.05). However, the preoperative numerical rating scale (NRS) score was significantly higher in group A than in group B (P<0.05). Postoperative pain relief was evaluated using the NRS and VAS scores. At last follow-up, high-frequency ultrasonography was performed to assess the morphology of the nerve coaptation site, blood flow signals, and recurrence of PSN. Results All patients in both groups were followed up, the follow-up time was (11.38±1.34) months in group A and (11.71±1.60) months in group B, with no significant difference between the two groups (t=?0.583, P=0.564). In both groups, the VAS and NRS scores before discharge and at last follow-up improved when compared with the preoperative scores, and further improvement was observed over time after surgery; all differences were significant (P<0.05). There was no significant difference between the two groups in the VAS or NRS scores before discharge, or in the NRS score at last follow-up (P>0.05). However, at last follow-up, the VAS score was significantly lower in group A than in group B (P<0.05). At last follow-up, PSN recurrence occurred in 1 patient in group A, with an NRS score of 2. In group B, high-frequency ultrasonography revealed hypoechoic nodular thickening at the original nerve coaptation site, sparse blood flow signals, and an increased cross-sectional area compared with the proximal segment of the same nerve in 3 patients, suggesting neuroma-like changes; however, none of these patients had residual limb pain. No PSN recurrence was detected in the remaining patients. Postoperatively, 1 patient in group A developed paresthesia around the surgical incision, and 3 patients in group B experienced delayed incision healing. Twenty-two patients were successfully fitted with prostheses. ConclusionTMR combined with SGA and EST sleeve coaptation can relieve pain to some extent in the treatment of post-amputation PSN. TMR targeting sensory nerves may show a trend toward better pain control; however, further validation is still required.