OBJECTIVES: The Rasch-built Overall Disability Scale (R-ODS) was initially designed and validated to measure activity and social participation limitations in patients with immune-mediated peripheral neuropathy. The objective of this research was to generate evidence on the measurement properties of the R-ODS in patients with symptomatic hereditary ATTR amyloidosis (hATTR amyloidosis) with polyneuropathy. METHODS: Assessments (n=359) of the 24 R-ODS items were collected in the patisiran phase 2 open-label extension (OLE, NCT01961921) and the APOLLO phase 3 placebo-controlled trials (NCT01960348). Trial participants were symptomatic hATTR patients with polyneuropathy, including a broad range of disease severity as measured by mobility impairment and broad range of underlying genetic mutations. The data underwent a comprehensive psychometric analysis based on Rasch Measurement Theory. RESULTS: R-ODS items covered a wide spectrum of activity and social participation limitations that essentially captured the significant breadth of limitations observed in the patient sample (96% of the range covered). However, the coverage of the part of the continuum corresponding to the lowest levels of limitation (i.e. the most “difficult” activities) could be improved. The 3-point response scale of the R-ODS was appropriate, as all response options for all items were correctly ordered. Most items showed acceptable fit to the Rasch model. The reliability of the R-ODS measure was good (Person Separation Index: 0.95). Item responses were stable between subgroups (age, gender, global region, genotype), with a very small number of items showing Differential Item Functioning, mostly between global regions. CONCLUSIONS: Overall, the R-ODS is an appropriate measure of activity and social participation limitations in hATTR patients with polyneuropathy. Further research is needed to understand and assess the tool’s sensitivity to detect changes in these limitations over time.