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Objective: To standardize a method to measure cognitive fatigue in patients with multiple sclerosis (MS)., Background: Many patients with MS complain of cognitive fatigue, defined as a decline in cognitive performance during a task requiring sustained activity. Until now there has not been a standardized way to detect cognitive fatigue or determine its severity., Methods: We administered the Paced Auditory Serial Addition Test (PASAT) to 130 normal controls and 100 randomly selected patients with MS, and compared the number of correct responses between the first third and last third of the test., Results: The controls averaged 2 more correct responses in the last third of the PASAT than in the first third. The patients with MS averaged 2 to 3 fewer correct responses in the last third than the first third., Conclusions: Our study showed that comparing responses between the first and last thirds of the PASAT is a reliable method to measure cognitive fatigue in patients with MS. We also present normative data to be used to determine whether patients with MS have cognitive fatigue.