Comparison of Reoperation and Complication Rates Between Acute and Delayed Advanced Nerve Interface Procedures in Lower-Extremity Amputees

<b>Background/Objectives</b>: Targeted muscle reinnervation and regenerative peripheral nerve interface procedures have emerged as effective techniques for reducing post-amputation pain and preventing symptomatic neuroma formation. However, the optimal timing of these procedures remains debated. This study aims to compare complication and reoperation rates between acute and delayed advanced nerve interface procedures in lower-extremity amputees. <b>Methods</b>: A retrospective cohort study was conducted including 74 patients who underwent acute or delayed targeted muscle reinnervation and/or regenerative peripheral nerve interface procedures between 2019 and 2025 at a tertiary academic medical center. Procedures performed concurrently with amputation or during early-stage reconstruction were classified as acute, whereas procedures performed more than one month after amputation were classified as delayed interventions. The primary outcome was postoperative surgical complications occurring within one year. Mann-Whitney U and chi-square tests were used for group comparisons. Univariable and multivariable logistic regression analyses were performed to identify factors associated with surgical complications, adjusting for potential confounders. A <i>p</i>-value < 0.05 was considered statistically significant. <b>Results</b>: Of 80 limbs, 47 (58.8%) underwent acute and 33 (41.3%) underwent delayed procedures. One-year complication rates were 23.4% in the acute group, and 12.1% in the delayed group, with wound-related complications predominantly occurring in patients undergoing amputation for infection or vascular disease. Unexpected reoperation rates were 19.1% for acute and 12.1% for delayed interventions. On univariable and multivariable analyses, early procedures demonstrated higher odds of surgical complications. However, these associations did not reach statistical significance and were limited by baseline differences in patient comorbidity and etiology. <b>Conclusions</b>: Early advanced nerve interface procedures were performed in more medically complex patients and were associated with higher observed rates of surgical complications, whereas delayed procedures were associated with a higher incidence of recurrent symptomatic neuromas. These findings underscore the importance of patient selection, etiology of amputation, and surgical context, rather than timing alone, when determining the optimal approach to nerve interface reconstruction following lower-extremity amputation.