Objective To investigate the psychometric properties of the Multiple Sclerosis Impact Scale (MSIS-29) and to assess the relationship between the Kurtzke Expanded Disability Status Scale and the physical and psychological parts of this score. Methods A population-based study identified cases with definite multiple sclerosis (MS) in the north-east region of Ireland. They were examined and completed the MSIS-29. Cases were classified as mild (Expanded Disability Status Score (EDSS) 0–3.0), moderate (EDSS 3.5–5.5), or severe (6.0–9.5) MS. Results The 248 participants (82 male, 166 female) had a mean age of 49.1 years (SD 12.4). EDSS ranged from 0 to 9.5 (median 6.0). Data quality was excellent (0.02% missing data), physical and psychological scores spanned the entire range with low floor and ceiling effects. Internal consistency was high (Cronbach’s alpha 0.97 – physical score, 0.93 – psychological score). The convergent validity of the physical impact score of the MSIS-29 with the Kurtzke EDSS was confirmed with a high Spearman’s rank coefficient correlation of 0.63 ( P = 0.01). Physical impact scores for mild, moderate, and severe disability as were statistically different at 25.9%, 48.0%, and 63.9%, respectively. Mean psychological score was non-significantly higher in the moderately disabled group at 47.4% compared with the severely disabled at 44.3% ( P = 0.58). Conclusions The MSIS-29 is an acceptable, reliable, and valid method of recording quality of life. A significant relationship between higher physical impact scores of the MSIS-29 and higher Kurtzke EDSS values suggests that is may be of use in clinical trials to monitor progression.