Background/Aims: Appropriate and timely screening instruments that sensitively capture the cognitive functioning of multiple sclerosis (MS) patients are the need of the hour. We evaluated newly derived regression-based norms for the Symbol Digit Modalities Test (SDMT) in a Dutch-speaking sample, as an indicator of the cognitive state of MS patients. Methods: Regression-based norms for the SDMT were created from a healthy control sample (n = 96) and used to convert MS patients' (n = 157) raw scores to demographically adjusted Z-scores, correcting for the effects of age, age2, gender, and education. Conventional and regression-based norms were compared on their impairment-classification rates and related to other neuropsychological measures. Results: The regression analyses revealed that age was the only significantly influencing demographic in our healthy sample. Regression-based norms for the SDMT more readily detected impairment in MS patients than conventional normalization methods (32 patients instead of 15). Patients changing from an SDMT-preserved to -impaired status (n = 17) were also impaired on other cognitive domains (p < 0.05), except for visuospatial memory (p = 0.34). Conclusions: Regression-based norms for the SDMT more readily detect abnormal performance in MS patients than conventional norms, identifying those patients at highest risk for cognitive impairment, which was supported by a worse performance on other neuropsychological measures.