Introduction <p>Hereditary transthyretin amyloidosis (ATTRv amyloidosis) is a severe, autosomal dominant disease resulting from multisystemic extracellular deposition of amyloid fibrils, leading to progressive organ damage and death. Sudoscan is a reproducible tool investigating sweat gland function and, indirectly, small nerve fiber impairment. The aim of this study was to evaluate any changes over time in electrochemical skin conductance (ESC) measured by Sudoscan in a cohort of late-onset patients with ATTRv from a single Italian center. Additionally, we investigated the role of Sudoscan as a marker of disease severity to confirm previous literature data.</p> Methods <p>We enrolled 61 patients with a late-onset ATTRv amyloidosis harboring different <i>TTR</i> variants with at least one clinical and instrumental evaluation including Sudoscan. Correlations with clinical data (including both clinical scales and questionnaires) were investigated to confirm the role of Sudoscan as a marker of disease severity. Moreover, a longitudinal analysis was performed in the subgroup of patients with at least 4 complete yearly&#xa0;evaluations (<i>n</i> = 23) to assess the role of Sudoscan as a marker of disease progression.</p> Results <p>At each yearly assessment, ESC values from both feet and hands significantly correlated with disease duration and neuropathy severity, as assessed by common clinical scales and questionnaires. No correlation was found with age at evaluation. Moreover, we observed a statistically significant change over time in ESC values measured at the feet (fESC) but not at&#xa0;the hands (hESC).</p> Conclusions <p>Sudoscan may represent a reliable marker of dysautonomia in ATTRv amyloidosis, displaying a potential role as a marker of both disease severity and progression. It could, therefore, serve as an outcome measure in future clinical trials. In addition, feet ESC seems to be a significant, independent predictor of autonomic dysfunction.</p>