Background: The minimal important change (MIC) of the 6-minute walk test (6MWT) is not clear for patients with Multiple Sclerosis (MS), hampering treatment evaluation. The aim of our study was therefore to determine the MIC of the 6MWT in MS patients. Methods: MS patients did the 6MWT using the instruction to walk at comfortable speed twice with approximately one year in between. After the second 6MWT they completed 3-point anchor question. The MICadjusted with a 95% confidence interval (CI) was calculated with the predictive modelling method with bootstrapping. Results: 118 MS patients (mean age 48.2 years, 23.7% men) were included between September 2018 and October 2019. Mean 6MWT distance was 468 ± 112 m at baseline and 469 ± 115 m one year later. Twenty-three (19.5%) patients answered their walking distance improved, 43 (36.4%) answered it worsened. A MICadjusted for improvement of 19.7 m (95%CI 9.8–30.9 m) was found, and for deterioration of 7.2 m (95%CI -3.3–18.2 m). Conclusions: Using the most sophisticated statistical method, the MICadjusted of the 6MWT in MS patients was 19.7 m for improvement, and 7.2 m for deterioration. This knowledge allows physiotherapists and physicians to evaluate if their treatment has led to a meaningful improvement for their MS patients or if walking of their patients has deteriorated.