Background: Axonal damage and inflammatory demyelination both occur in multiple sclerosis (MS). Some studies suggest that statins, through pleiotropic effects, reduce inflammatory episodes and protect neurons. However, other studies suggest statins have disparate impacts on these pathologic processes. Objective: The objective of this study was to assess disability progression in MS patients receiving statin therapy. Methods: We performed a retrospective medical record review of an established population-based MS prevalence cohort in Olmsted County, Minnesota, comparing disability progression between patients receiving statins and controls. Results: Duration of statin use ranged from 1.9 to 20.3 years with a mean and standard deviation of 6.8 ± 4 years. Years between assessments ranged from 0.6 to 8.2 (75% of patients having intervals >6.4 years). The median (interquartile range) absolute change of disability among the statin group was 0 (0 to +1), compared with +0.5 (0, +1) in the no-statin group. Distributions were not significantly different ( p = 0.39). The mean (standard deviation) absolute change of disability scores among the statin group was +0.69 (+1.49), not significantly different from +0.61 (+1.31) in the no-statin group. Likewise, annualized disability scores did not differ significantly ( p = 0.23). Eighteen (40%) patients worsened by 1.0 or more on Expanded Disability Status Scale (EDSS) in the statin group and 36 (40%) in the no-statin group ( p = 0.85, chi-squared test). Conclusions: In this cohort, disability progression did not differ between those receiving statin therapy and controls. These findings support the hypothesis that statins, in doses currently prescribed for hyperlipidemia, do not affect the long-term course of MS.