Objective: To explore the feasibility and effects of a computer-assisted cognitive rehabilitation intervention – Memory, Attention, and Problem Solving Skills for Persons with Multiple Sclerosis (MAPSS-MS) – for persons with multiple sclerosis on cognitive performance, memory strategy use, self-efficacy for control of symptoms and neuropsychological competence in activities of daily living (ADL). Design: A randomized controlled single-blinded trial with treatment and wait list control groups. Setting: Southwestern United States. Subjects: Convenience sample of 61 persons (34 treatment, 27 wait list control) with multiple sclerosis (mean age 47.9 years, SD 8.8). Intervention: The eight-week MAPSS-MS intervention program included two components: (a) eight weekly group sessions focused on building efficacy for use of cognitive compensatory strategies and (b) a computer-assisted cognitive rehabilitation program with home-based training.Outcome measures: A neuropsychological battery of performance tests comprising the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) and self-report instruments (use of memory strategies, self-efficacy for control of multiple sclerosis and neuropsychological competence in ADL) were completed at baseline, two months (after classes), and at five months. Results: Both groups improved significantly (P < 0.05) over time on most measures in the MACFIMS battery as well as the measures of strategy use and neuropsychological competence in ADL. There was a significant group-by-time interaction for scores on the measures of verbal memory and the use of compensatory strategies. Conclusions: The MAPSS-MS intervention was feasible and well-accepted by participants. Given the large relative increase in use of compensatory strategies by the intervention group, it holds promise for enhancing cognitive function in persons with multiple sclerosis.