Multiple sclerosis (MS) is a disease of the central nervous system where roughly 50% of patients exhibit cognitive impairment. Episodic memory defects are particularly common in MS and the California Verbal Learning Test: 2nd Edition (CVLT-II) was recommended for assessment in MS in a recently published consensus position paper. We investigated the validity of the CVLT-II in 351 MS patients and 69 demographically matched normal controls. MS patients performed significantly more poorly on 18 of the 23 measures examined. In addition to a general memory factor, factor analysis revealed five distinct factors conforming to measures of consolidation, primary/recency effect, proactive interference, and learning asymptote. The external validity of the CVLT-II was also supported by logistic regression analysis, which separated employed from work-disabled MS patients. We conclude that the CVLT-II is a valid test in MS and provides a rich constellation of verbal memory measures.