Background: Cognitive dysfunction affects 40% to 70% of people with multiple sclerosis (MS). Sex may influence a person's cognition. Although a few studies have reported greater cognitive deficits in men than women, it is unclear whether specific cognitive domains are more vulnerable than others to the effects of sex or whether cognition is influenced by neurologic or psychiatric variables., Methods: A chart review was undertaken of 408 people with MS referred to neuropsychological services. Demographic and MS-related variables were extracted from the patients' records. We used the Minimal Assessment of Cognitive Functioning in Multiple Sclerosis for the neuropsychological assessment. Raw test scores were converted to z scores using Canadian regression-based normative means. A general linear model was conducted on the adjusted scores, controlling for age; years of education; disease course; illness duration; and disability, anxiety, and depression scores., Results: Men were more likely than women to have primary progressive MS (χ=6.415, P=0.011). There were no other sex differences with respect to demographic, neurologic, or psychiatric data. Women performed significantly better than men on the California Verbal Learning Test-Second Edition Total Learning index (F=7.846, P=0.006)., Conclusions: An analysis of a large, consecutive sample of people with MS demonstrated that sex, independent of demographic, neurologic, or psychiatric factors, is an important determinant in cognitive impairment, with men being more impaired than women on tests of verbal learning and memory.