Background and objectives: The Symbol Digit Modalities Test (SDMT) shows advantages over the Paced Auditory Serial Addition Test (PASAT) as a cognitive test in patients with multiple sclerosis (MS). To determine which of these tests is most valid and reliable over time as an indicator of the cognitive state of MS patients, long-term test results of both tests were compared in relation to scores of the Brief Repeatable Battery of Neuropsychological tests (BRBN). Methods: For 485 MS patients visiting the VU University Medical Center Amsterdam for different research projects, a total number of 1078 visits with BRBN (including PASAT and SDMT) was planned. Observed and model-based correlations were used to calculate the construct validity of the SDMT and PASAT 3 seconds test (PASAT3) by comparing correlations with the BRBN-sumscore. The test-retest reliability of each test was also computed. Results: For the construct validity, higher correlations were found between SDMT and BRBN compared to PASAT3 and BRBN, especially for the model-based correlations at baseline. The reliability of the measurements was good for all instruments, with the highest coefficients for the SDMT. Conclusion: As a single assessment tool for cognition in MS, the SDMT is more valid and reliable compared to PASAT3. © The Author(s) 2013.