Multiple Sclerosis (MS) is associated with MRI signal alteration and neuropsychological (NP) dysfunction. Screening tools have been developed to identify patients at high risk for these neurological complications of MS. One such measure, the Multiple Sclerosis Neuropsychological Screening Questionnaire (MSNQ), has well-established reliability and predictive validity. In this article, we report on the accumulated findings derived from 162 consecutive research participants and MS clinic attendees. Our data show significant correlation between both patient- and informant-report MSNQ and NP impairment. As shown previously, larger, and more significant correlations are found between informant-report MSNQs than with patient-report MSNQs. In addition, we find that the MSNQ predicts follow-up NP testing 51 weeks after baseline with a similar degree of association. Finally, the MSNQ is correlated with MRI measures of whole-brain lesion burden and atrophy, secondary progressive course, and vocational disability. We conclude that the MSNQ is reliable and valid for detecting neuropsychological and neuropsychiatric complications of MS.