Backgrounds Considering the lack of screening technology that would permit neurologists to identify patients who may benefit from formal or more comprehensive assessment of neuropsychological status in patients with multiple sclerosis (MS) in Argentina, we felt the need to validate the Multiple Sclerosis Neuropsychological Screening Questionnaire (MSNQ) developed by Benedict, et al. Objective The objective in this multicenter study was to test the reliability and validity of the MSNQ after translation into Spanish in Argentina. We also compared the MSNQ yield by the patient report with that of the two different informants. The sample included 125 patients with MS and 36 normal controls, 27 patients had two informants available and 23 patients and their informants were examined twice at 1-week intervals (test–retest group). All participants completed the MSNQ, RAO BRB, Beck Depression Inventory-Fast Screen, EDSS, and MS Functional Composite. Results We found that an MSNQ-I score of 26 or more resulted in classifications yielding sensitivity of 0.91 and specificity of 0.80, suggesting some utility for this Argentine, informant-report measure. Conclusions This Spanish version of the MSNQ is reliable and useful as a screening test for identifying patients at high risk for cognitive impairment in MS.